The effect of pain associated with

delayed onset muscle soreness on the

autonomic nervous system as measured
by heart rate variability

Larissa Morgan

A dissertation submitted in partial fulfilment of the

requirements for the Master of Osteopathy,
Unitec Institute of Technology New Zealand, 2008

Acknowledgements

The following work represents a lengthy collaborative effort; therefore Id first like to
gratefully acknowledge my supervisors Robert Moran and Dr Craig Hilton for their
contribution, guidance, and patient support in honing this project and bringing it to
completion. Gratitude and recognition are also extended to all my colleagues and
friends, who every week kept me going with feedback, counsel, unending cups of tea,
and much needed comic relief. To my family, thank you does not adequately
express my appreciation for the unwavering support and encouragement you have
given me, which has in no small measure contributed to my achievements. Lastly, to
Tui, who knew exactly what time to sit between me and the monitor thank you for
reminding me when to have a break.

Table of Contents
ACKNOWLEDGEMENTS-------------------------------------------------------------------------------------- 2
TABLE OF CONTENTS----------------------------------------------------------------------------------------- 3
LIST OF FIGURES ----------------------------------------------------------------------------------------------- 5
LIST OF TABLES------------------------------------------------------------------------------------------------- 6
ABBREVIATIONS------------------------------------------------------------------------------------------------ 7
INTRODUCTION ------------------------------------------------------------------------------------------------- 8
BACKGROUND ---------------------------------------------------------------------------------------------------- 8
RESEARCH QUESTION ------------------------------------------------------------------------------------------- 13
SECTION 1: LITERATURE REVIEW---------------------------------------------------------------------- 14
CONCEPTS WITHIN OSTEOPATHY ------------------------------------------------------------------------------ 14
THE AUTONOMIC NERVOUS SYSTEM ------------------------------------------------------------------------- 19
Introduction-------------------------------------------------------------------------------------------------- 19
Influences on autonomic function ------------------------------------------------------------------------- 22
Indicators of autonomic function ------------------------------------------------------------------------- 23
Heart Rate Variability -------------------------------------------------------------------------------------- 24
Influences on heart rate variability ----------------------------------------------------------------------------- 25
Measurement and parameters of heart rate variability -------------------------------------------------------- 28
Limitations of heart rate variability as an indicator of ANS activity ---------------------------------------- 30

PAIN -------------------------------------------------------------------------------------------------------------- 33
Introduction-------------------------------------------------------------------------------------------------- 33
Physiological or sensory dimension of pain ------------------------------------------------------------- 33
Affective or emotional dimension of pain ---------------------------------------------------------------- 34
The autonomic nervous system and pain----------------------------------------------------------------- 35
Delayed onset muscle soreness---------------------------------------------------------------------------- 37
Physiology of delayed onset muscle soreness ----------------------------------------------------------------- 37
Delayed onset muscle soreness as a model of pain ----------------------------------------------------------- 40

SUMMARY AND AIMS OF RESEARCH--------------------------------------------------------------------------- 42

REFERENCES---------------------------------------------------------------------------------------------------- 43
SECTION 2: MANUSCRIPT ---------------------------------------------------------------------------------- 56
ABSTRACT ------------------------------------------------------------------------------------------------------- 59
INTRODUCTION -------------------------------------------------------------------------------------------------- 60
METHODS -------------------------------------------------------------------------------------------------------- 62
Design -------------------------------------------------------------------------------------------------------- 62
Subjects------------------------------------------------------------------------------------------------------- 62
Variables and Operational Definitions------------------------------------------------------------------- 63
Independent variable --------------------------------------------------------------------------------------------- 63
Dependant variable----------------------------------------------------------------------------------------------- 63

Procedure ---------------------------------------------------------------------------------------------------- 64
Intervention ------------------------------------------------------------------------------------------------------- 65

DATA ANALYSIS ------------------------------------------------------------------------------------------------ 66

Data extraction ---------------------------------------------------------------------------------------------- 66
RESULTS --------------------------------------------------------------------------------------------------------- 69
Induction of pain associated with DOMS as measured by VAS--------------------------------------- 70
Normalised high frequency parameter of heart rate variability -------------------------------------- 71
Phase A Baseline HF HRV data ------------------------------------------------------------------------------ 72
Phase B pre-DOMS, DOMS and recovery period HF HRV data------------------------------------------ 72

Normalised low frequency parameter of heart rate variability --------------------------------------- 75

Phase A Baseline LF HRV data ------------------------------------------------------------------------------ 75
Phase B pre-DOMS, DOMS and recovery period LF HRV data ------------------------------------------ 75

DISCUSSION ------------------------------------------------------------------------------------------------------ 79
Outcomes----------------------------------------------------------------------------------------------------- 79

Delayed onset muscle soreness as a model of pain ----------------------------------------------------------- 79

Heart rate variability --------------------------------------------------------------------------------------------- 81

Related research -------------------------------------------------------------------------------------------- 83

Cognitive and physiological influences on the ANS and on pain ------------------------------------- 84
Limitations and weaknesses ------------------------------------------------------------------------------- 88
CONCLUSION ---------------------------------------------------------------------------------------------------- 91
ACKNOWLEDGMENTS ------------------------------------------------------------------------------------------- 92
REFERENCES---------------------------------------------------------------------------------------------------- 93
APPENDIX A: SUBJECT CONSENT FORM ----------------------------------------------------------- 101
APPENDIX B: SUBJECT INFORMATION SHEET --------------------------------------------------- 102
APPENDIX C: OPERATIONAL INSTRUCTIONS ---------------------------------------------------- 104
APPENDIX D: DOMS INFORMATION SHEET ------------------------------------------------------- 105
APPENDIX E: INTERNATIONAL JOURNAL OF OSTEOPATHIC MEDICINE GUIDE
FOR AUTHORS ------------------------------------------------------------------------------------------------ 106

List of Figures
SECTION 1: LITERATURE REVIEW
FIGURE 1
FIGURE 2
FIGURE 3

ORGANISATION OF THE NERVOUS SYSTEM.---------------------------------------- 19

STRUCTURE OF THE AUTONOMIC NERVOUS SYSTEM.-------------------------- 20
NORMAL ELECTROCARDIOGRAM WAVEFORM------------------------------------ 24

SECTION 2: MANUSCRIPT
FIGURE 1
FIGURE 2
FIGURE 3
FIGURE 4

OVERVIEW OF STUDY DESIGN------------------------------------------------------- 63

TYPICAL HEART RATE VARIABILITY ANALYSIS REPORT------------------ 66
HIGH FREQUENCY HRV AND VAS VERSUS TIME------------------------------ 73
LOW FREQUENCY HRV AND VAS VERSUS TIME------------------------------- 76

List of Tables
TABLE 1
TABLE 2

EXERCISE SUMMARY FOR ALL SUBJECTS------------------------------------------- 65

SUBJECT CHARACTERISTICS------------------------------------------------------------- 69

Abbreviations
AMI

Acute myocardial infarction

ANS

Autonomic nervous system

DOMS

Delayed onset muscle soreness

ECG

Electrocardiogram

HF

High frequency

HPA

Hypothalamic-pituitary-adrenal

HRV

Heart rate variability

LF

Low frequency

MTJ

Musculotendinous junction

PSD

Power spectral density

RSA

Respiratory sinus arrhythmia

SA

Sinoatrial

ULF

Ultra-low frequency

VLF

Very low frequency

Introduction
The Review of Literature commences with a background in which historical and
contemporary concepts within the osteopathic profession are outlined, before the main
body of the review which discusses the following topics: concepts within osteopathy;
the autonomic nervous system; and pain.

Background
Spinal manipulation is a form of treatment practised in the manual therapy professions
(e.g. chiropractic, osteopathy, and physiotherapy). Although not formally defined,
many within the manual therapy professions would describe spinal manipulation as
the application of a high-velocity low-amplitude force to the zygopophyseal joint of a
specific spinal segment, which results in cavitation of that joint and is often
accompanied by an audible cracking or popping sound (Gibbons & Tehan, 2006).

Within osteopathy there are an abundance of historical and contemporary anecdotal

claims that spinal manipulation benefits health. Reported health benefits include
reduced pain, greater freedom of movement, and overall improvement in function.
Thus far, however, the physiological mechanisms of spinal manipulation have not
been fully elucidated (see reviews by Evans (2002) and Pickar (2002)), and there is
little evidence to support the effectiveness of spinal manipulation in any medical
condition (see 2006 review by Ernst & Canter). Nonetheless, many osteopaths
maintain the long held belief that the autonomic nervous system (ANS) provides one
of the links1 between their manual therapeutic techniques, and many of the reported
health benefits. The application of spinal manipulation and other techniques within
osteopathy is partly based on a central tenet presented within many osteopathic texts,
namely, that musculoskeletal or visceral disturbance can have effects elsewhere in the
body via the ANS (DiGiovanna, Schiowitz, & Dowling, 2005; Kuchera & Kuchera,
1993; Parsons & Marcer, 2006; Stone, 1999).

Other claimed links between osteopathic manual techniques and reported health benefits include improved biomechanical
efficiency, and improved blood supply and drainage.

The autonomic mechanisms which mediate interaction between musculoskeletal and

visceral structures are usually named autonomic reflexes. Early researchers in this
field focused on end-organ effects and as such the reflexes were described as somatovisceral, viscero-somatic, viscero-visceral and somato-somatic (Beacham & Perl,
1964; Sato & Schmidt, 1971). Although use of the word somatic varies between
professional disciplines,2 here the term somatic refers to the musculoskeletal tissues of
the body as distinct from viscera or some other entity such as the mind or the
environment ("The new Collins dictionary and thesaurus," 1988). Within osteopathic
literature the term musculoskeletal is frequently interchanged with the term
somatic to describe the tissues of the human frame. Many viscero-visceral reflexes
have been well investigated, for example the arterial baroreceptor reflex for blood
pressure and the continence and micturition reflex of the urinary bladder (Janig &
Habler, 1995). Less understood are the mechanisms responsible for viscero-somatic,
somato-visceral, and somato-somatic reflexes (Bielefeldt & Gebhart, 2006). Yet,
despite a rudimentary understanding, these reflexes and their purported clinical
significance remain a fundamental concept within osteopathic texts and undergraduate
education of osteopaths.

Within osteopathic theory, a visceral or somatic disturbance is said to perturb signals

within local autonomic fibres. The signals from these fibres then converge onto the
associated autonomic ganglia, many of which reside in close proximity to related
vertebral segments. The aberrant input into the autonomic ganglia is purported to
activate a reflex that alters signalling in autonomic fibres to other structures common
to the same autonomic segment. Although not demonstrated in experimental studies,
this osteopathic concept suggests that a low back dysfunction, for example, can affect
lower abdominal and pelvic organ function through a somato-visceral reflex.
Similarly, it has been claimed that poor respiratory function could manifest in
segmental and palpatory changes in the mid-thoracic region through a viscero-somatic
reflex (Kuchera & Kuchera, 1993; Parsons & Marcer, 2006).

Somatic: from the Greek Somatiks, meaning of the body. 1. of or relating to the soma: somatic cells (e.g. cells or tissue that
resides outside the germline). 2. of or relating to an animal body or body wall as distinct from the viscera, limbs, and head. 3. of
or relating to the human body as distinct from the mind: a somatic disease ("The new Collins dictionary and thesaurus," 1988).

As described by osteopaths, these concepts have lacked experimental support and

have generated limited interest from researchers. A small number of clinical studies
have shown that visceral disease may manifest in sensory, autonomic, and
skeletomotor changes (Beal, 1985; Bonica, 1992; Janig & Habler, 1995). Some
clinicians have reported that visceral disease is accompanied by palpable
musculoskeletal changes, and have further suggested that these changes may be useful
for diagnosis and evaluation of treatment efficacy (Beal, 1983; Cox, Gorbis, Dick,
Rogers, & Rogers, 1987; Nicholas et al., 1985).

More recently, an association between Type II diabetes mellitus and palpable skin
texture change was reported (Licciardone, Fulda, Stoll, Gamber, & Cage, 2007).
Licciardone et al. found the strongest and most consistent of the palpatory findings
assessed (skin changes, trophic changes, tissue changes, tenderness, immobility), to
be tissue changes on the right side of T11-L1 vertebral segments. Yet, many of the
five palpatory elements assessed showed little difference between right and left, even
though much of the pancreas is located left of the bodys midline. Furthermore, the
most consistent skin texture changes were found at the level of T11-L1, a segmental
level beyond the autonomic supply of the pancreas presented in many undergraduate
physiology texts (T6-T10). Licciardone et al. speculated that reflex viscerosomatic
changes directly related to the progression of type Type 2 diabetes mellitus might be
responsible for the results, but could not eliminate the possibility of a spurious
association or chance observation. Based on sparse and inconclusive literature, the
link between visceral disease and musculoskeletal changes is not a clear and causal
one, and could be considered associative at best. Moreover, if frank pathology does
not manifest in consistent or clearly observable musculoskeletal changes, the
osteopathic concept that non-pathological disturbance may result in similar change is
less plausible.

Although the causality between visceral disease and musculoskeletal change is

unclear, there is evidence of an interaction between visceral and musculoskeletal
structures. The referred pain phenomenon is the most clinically recognised and
investigated interaction between visceral and somatic tissues. The International
Association for the Study of Pain describes referred pain in neurological terms as
pain perceived as arising or occurring in a region of the body innervated by nerves or
10

branches of nerves other than those that innervate the actual source of pain, or in
clinical terms as pain perceived as occurring in a region of the body topographically
distinct from the region in which the actual source of pain is located (Merskey &
Bogduk, 1994, p. 12).

Referred pain is not an autonomic reflex although may be associated with such
reflexes. As a phenomenon, referred pain has long been recognised, with descriptions
dating to the late 19th century (Ross, 1888, Ruch, 1961, & Sturge, 1883, as cited in
Arendt-Nielsen & Svensson, 2001). Several theoretical models have been developed
to explain the occurrence of referred pain, with the current and most accepted model
being the convergence-projection theory (Arendt-Nielsen & Svensson, 2001). This
theory is broadly similar to the osteopathic concept regarding autonomic reflexes in
that the proposed mechanism is one of convergence. Although not wholly
understood, referred pain is thought to occur by the following means: pain signals
from injured tissue and normal sensory signals from other tissues converge within the
dorsal horn of common spinal segments, however, in the barrage of information, the
spinal cord cannot clearly distinguish the origin of the pain signal, and so a noninjured area is perceived to be painful (Arendt-Nielsen, Laursen, & Drewes, 2000;
Arendt-Nielsen & Svensson, 2001; Giamberardino, Affaitati, Lerza, & Vecchiet,
2000). Due to the clinical significance of referred pain (e.g. myocardial ischemia and
pain in the left arm), this phenomenon is the most widely acknowledged and studied
interaction between somatic and visceral structures.

In contrast to the referred pain phenomenon, the concept that somatic and visceral
disturbance can influence other structures though the ANS has limited scientific
support. With few human studies available, osteopathic literature has often relied on
evidence from experiments on laboratory animals. Conclusions from these
experiments, which are cited frequently and with little critique in osteopathic
literature, are that stimulation of visceral and somatic nerves produce responses in
cardiac ANS activity (Terui & Koizumi, 1984), and that noxious or painful
musculoskeletal stimuli clearly and consistently modulate ANS activity and
sometimes visceral function (Adachi, Meguro, Sato, & Sato, 1990; Kaufman, Sato,
Sato, & Sugimoto, 1977; Sato, Sato, & Schmidt, 1997; Sato & Schmidt, 1987). Many
of the same investigators have also found that innocuous mechanical stimuli affect the
11

ANS, albeit in a milder and less consistent manner than noxious stimuli (Sato et al.,
1997; Sato & Swenson, 1984). Yet, within osteopathic literature, the findings
regarding innocuous stimulation on the ANS are cited infrequently, potentially
exposing a bias towards citing scientific data that supports osteopathic concepts.

More recently, osteopathy and other manual therapies have begun to formally
investigate whether manual therapeutic techniques influence the ANS. Evidence has
emerged showing that spinal manipulation and innocuous non-spinal stimulation
affect autonomic activity (Budgell & Hirano, 2001; Budgell & Polus, 2006; Cooper,
2006; Driscoll & Hall, 2000; Eingorn & Muhs, 1999; Knutson, 2001; McGuiness,
Vicenzino, & Wright, 1997; Zhang, Dean, Nosco, Strathopulos, & Floros, 2006);
however, clinical outcomes have not been included in these studies. To date, studies
have focused on the cause-effect relationship between manual therapy techniques and
the ANS without regard to magnitude of effect, and whether such effect is clinically
favourable or unfavourable. Furthermore, the investigations have not ascertained
whether techniques that are purported to modulate the ANS are a necessary, or
clinically relevant, part of care. The issue of clinical relevance is further weakened by
insufficient critical review of the findings: any ANS effects observed in these
investigations could be epiphenomena and not part of the causal chain purported to
exist between musculoskeletal disturbance and effects elsewhere in the body.

On balance, the osteopathic concept that musculoskeletal disturbance can perturb the
ANS is lacking support. The poorly elucidated mechanisms, inadequate appraisal of
clinical relevance, and limited scope of research places the concept in a contentious
light despite associations suggested by current literature (Licciardone et al., 2007).
It comes as no surprise then, as Stone (1999, p. 75) indicates in a contemporary
osteopathic text, that the concept of musculoskeletal irritation causing visceral
disturbance is not a recognised clinical entity. Yet, within osteopathic textbooks and
in oral history imparted in undergraduate training, the concept remains fundamental.
The osteopathic profession maintains the long held position that manual therapeutic
techniques favourably influence the ANS and are an appropriate part of care.

Dogma, coupled with limited and often inconclusive evidence, has done little to avert
any controversy surrounding the concept that somatic or visceral disturbance affects
12

the ANS. As such, several questions remain as it is yet to be established whether a

fundamental premise of osteopathic patient management has any basis: namely, does
ANS perturbation from mild to moderate musculoskeletal disturbance/injury occur?
Furthermore, the question is raised of whether it necessarily follows that such ANS
disturbance will have unfavourable clinical effects. If osteopathic techniques do
modulate ANS activity, can the techniques evoke an ANS response beyond any
localised or short-term general effects, to ameliorate the so-claimed effects further
afield? Although the impact of acute soft tissue injury on the ANS has been recently
investigated (Grimm, Cunningham, & Burke, 2005), there is a scant amount of
literature addressing these questions. There have been calls in the literature for a
definitive illustration of whether mild to moderate musculoskeletal disturbance could
have a deleterious impact on the ANS, and potentially on health and wellness.
Establishing the nature and significance of this link is important to not only evaluate
tenets within osteopathy, but may be of clinical relevance to those with acute injury or
those in chronic pain states.

Research question
The aim of this pilot study was to explore whether delayed-onset muscle soreness
(DOMS), as a model of pain and mild musculoskeletal injury, would affect the ANS
as measured by heart rate variability (HRV). The rationale for employing DOMS was
that it is simple to induce, non-invasive, and would simulate a soft tissue injury
without involving gross trauma or heterogeneity of damage.3 Heart rate variability
has been employed in a variety of fields to evaluate changes to the ANS, and although
not a direct measure of mean autonomic tone, HRV was considered a well supported
measure for this project.

Heterogeneity is used here to denote damage involving tissue types other than myofascia, such as bone, ligament, cartilage,
nerves, and blood vessels.

13

Section 1: Literature Review

Concepts within osteopathy
Within osteopathy, the terms philosophy, principle, and hypothesis are often
used in reference to the ideas put forward by founding members of the profession.
Based on review of osteopathic literature and dictionary definitions, the term
concept will be used to describe osteopathic ideas, and the term tenet to denote a
belief held in common by members of the osteopathic profession.

Within osteopathy, the approach to treatment is guided by several concepts, such as:

The body is a unit

Structure and function are reciprocally interrelated

The body possesses self-regulatory, repair, and defence mechanisms

The flow of body fluids is essential to health

(DiGiovanna et al., 2005, pp. 10-15; Kuchera & Kuchera, 1993, p. 2; Nelson,
2007b, pp. 6-11).
Although these concepts are not unique to osteopathy, they help form the basis of the
osteopathic perspective on health and disease.

Health, illness, and disease are concepts that differ between cultures and historically
have been rich with theory and debate. Osteopathic texts regard health and disease as
an interplay and balance between the emotional, chemical, and physical environments
(DiGiovanna et al., 2005, pp. 10-15; Kuchera & Kuchera, 1993, pp. 7-12; Stone,
1999, pp. 15-27). The notion within osteopathy is that failure to adapt, or exposure to
overwhelming external factors, can upset the balance between these environments and
can prevail over the bodys capacity for self-maintenance (DiGiovanna et al., 2005;
Stone, 1999). As a form of manual medicine, osteopathy emphasises the role the
neuromusculoskeletal system plays in the manifestation of health and disease
(DiGiovanna et al., 2005).

The concepts of normal function and dysfunction are commonly used within the
osteopathic profession. Yet, these terms are hampered in a similar manner as that of
health and disease. Stone (1999, pp. 28-56) has reasoned that disease may be

14

represented by a breakdown of communication between parts, and states that anything

interfering with cellular signalling efficiency may disrupt the ability to adapt. Within
osteopathy, this disruption is proposed to create a tendency towards disequilibrium,
disease, and dysfunction. Stones dialogue reflects content found in other osteopathic
texts (DiGiovanna et al., 2005; Kuchera & Kuchera, 1993; Ward, 2003), which assert
that neural, fluidic, or mechanical barriers to physiological communication can
influence the structure-function relationship. Thus, a general aim of osteopathic
treatment is to remove tissue barriers and allow better communication between parts
to re-establish itself (Stone, 1999, p. 32), in order to restore or maintain normal
function (Kuchera & Kuchera, 1993; Nelson, 2007b).

Correcting barriers to appropriate communication provides one of the rationales for

therapeutic techniques such as spinal manipulation. In a general sense, osteopaths
claim to address perceived aberration in neural processing by treating parts of the
body along the neural pathway that could be contributing to the dysfunction. The
concept of addressing aberrations in neural processing is based, in part, on the
structural distribution, widespread function, and anatomical relationships of the ANS.
The ANS is distributed throughout the entire nervous system and has the essential
function of maintaining homeostasis in conjunction with the respiratory, endocrine,
and immune systems. Anatomically, fibres of the sympathetic division of the ANS
are in close proximity to vertebral segments and associated soft tissues (muscle,
tendon, and ligament). Fibres of the sympathetic division of the ANS exit the spinal
cord between the first thoracic and second lumbar vertebra and are linked by a chain
of ganglia extending the length of the thoracic spine lateral to the same segments.

Theorists within osteopathy surmise that the anatomical arrangement of the ANS,
particularly the sympathetic division, makes the ANS accessible to osteopathic
manual treatment. For example, within osteopathy, the perceived accessibility of
sympathetic division permits the ANS to be influenced, albeit indirectly, with
techniques such as spinal manipulation. Although spinal manipulation has, in recent
times, been shown to have an effect on the ANS the mechanisms remain unclear
(Pickar, 2002; Willard, 2007; Wright, 1995). Nonetheless, many osteopaths maintain
the view that balance and integration of ANS subdivisions has a significant role in
health and disease, (DiGiovanna et al., 2005; Stone, 1999). As such, disturbance of a
15

body structure is considered by osteopaths to potentially perturb the balance between

ANS subdivisions, or lead to an aberration in autonomic neural processing, which
may influence other body structures with the same autonomic supply. This process is
succinctly described in a text by Parsons and Marcer (2006), who state that if a
spinal segment or any of the structures supplied by it are disturbed, convergence into
the common segment generates a reflex that may induce changes in any or all of the
structures supplied by that segment. However, the empirical consequences of this
process have not been fully drawn out and tested, such as whether the effects of these
autonomic reflexes can be objectively measured.

The functions of the musculoskeletal system are commonly regarded as being

locomotion, defence, support, and communication. The musculoskeletal, or somatic,
component of the body is considered by many osteopaths to be the final common
pathway by which we carry out our lives (Stone, 1999, p. 96), a concept echoed in
many contemporary osteopathic texts (DiGiovanna et al., 2005; Kuchera & Kuchera,
1993; Nelson, 2007a; Parsons & Marcer, 2006). Based on this view, osteopaths have
developed the concept of somatic dysfunction to denote alterations in the body as a
result of autonomic reflex mechanisms. From the Glossary of Osteopathic
Terminology the accepted definition of somatic dysfunction is an impaired or altered
function of related components of the somatic (body framework) system: skeletal,
arthrodial, and myofascial structures, and related vascular, lymphatic, and neural
elements (Glossary of Osteopathic Terminology, 2004).

The diagnosis of somatic dysfunction is based on subjective palpatory findings and

patient feedback.4 Anecdotal evidence suggests that patterns of somatic dysfunction
appear to follow ANS distribution although there is little scientific evidence to
support this notion. Somatic dysfunction is considered to contribute to the effect of
pathology, or be associated with pathology, however, osteopathic literature clearly
distinguishes somatic dysfunction from organic pathology and maintains that trauma,
4

Acute somatic dysfunction: Immediate or short-term impairment or altered function of related components of the somatic
(body-framework) system; characterised in early stages by vasodilation, oedema, tenderness, pain and tissue contraction
Chronic somatic dysfunction: impairment or altered function of related components of the somatic (body-framework) system,
characterised by tenderness, itching, fibrosis, paraesthesias, tissue contraction
Primary somatic dysfunction: 1) The somatic dysfunction that maintains a total pattern of dysfunction. 2) The initial or first
somatic dysfunction to appear temporally.
Secondary somatic dysfunction: somatic dysfunction arising either from mechanical or neurophysiologic response subsequent
to or as a consequence of other aetiologies (Glossary of Osteopathic Terminology, 2004)

16

degeneration, and inflammation are not considered somatic dysfunctions (DiGiovanna

et al., 2005, p. 16; Nelson, 2007a, pp. 12-13).

In order to ameliorate somatic dysfunction, one of the aims of osteopathic treatment

is to correct any interference the musculoskeletal system may have on autonomic
function (DiGiovanna et al., 2005; Kuchera & Kuchera, 1993; Parsons & Marcer,
2006; Stone, 1999). The supposition of a cause and effect relationship between the
ANS and musculoskeletal structures forms part of the rationale for the application of
spinal manipulation techniques to treat somatic dysfunction. Osteopath author Fred
Mitchell, Sr. illustrates this view when he noted that implicit in the term somatic
dysfunction is the notion that manipulation is appropriate, effective, and sufficient
treatment for it (Mitchell Jr., 1979), although none of these implicit assumptions (i.e.
suitability, efficacy, and adequacy) have been objectively demonstrated to date.

Osteopathic literature has begun to gather evidence on whether manual therapy

techniques such as spinal manipulation exert an influence on autonomic activity.
Several studies within both chiropractic and osteopathic literature have evaluated
spinal manipulation using a variety of outcome measures, including pain and ANS
indices. Researchers have found excitatory effects, such as changes in heart rate,
blood pressure, and respiratory rate (Knutson, 2001; McGuiness et al., 1997), altered
heart rate variability (Budgell & Polus, 2006), increased sudomotor activity (Simon,
Vicenzino, & Wright, 1997; Sterling, Jull, & Wright, 2001), increased skin
temperature (Sterling et al., 2001), altered cutaneous blood flow (Karason &
Drysdale, 2003), and post-manipulation hypoalgesia (Vicenzino, Collins, Benson, &
Wright, 1998). Different speed of manipulation has also demonstrated an effect on
the ANS (Chiu & Wright, 1996).

The ANS is also affected by non-manipulative stimulation of spinal segments, with

Sato and Swenson (1984) observing that ANS responses persisted beyond the
immediate post-application period (Budgell & Hirano, 2001; Fujimoto, Budgell,
Uchida, Suzuki, & Meguro, 1999; Moulson & Watson, 2006; Sato & Swenson, 1984;
Vicenzino, Cartwright, Collins, & Wright, 1998). Innocuous non-spinal stimulation
has also been documented to cause various autonomic changes (Cooper, 2006; Simon
et al., 1997). Despite these findings, however, the physiological processes to which
17

such effects may be attributed remain inconclusive. The diverging results seen in the
literature has prompted Pickar (2002) to suggest that more than one mechanism
likely explains the effects of spinal manipulation, and theories continue to abound
regarding what therapeutic processes or physiological mechanisms are involved
(Wright, 1995). Nonetheless, the effect of spinal manipulation on the ANS comprises
only one aspect within the concept that musculoskeletal or visceral disturbance can
perturb the ANS. Other aspects, such as whether ANS perturbation does occur and
can be objectively measured, or indeed is clinically relevant, have not been adequately
investigated.

In summary, a central tenet within osteopathy is that disturbance of a body structure

may perturb the ANS. Perturbation to the ANS is thought to influence other body
structures via common autonomic segments, and may result in somatic dysfunction.
The source of the autonomic perturbation, plus any subsequent effects on other
structures, is then thought to be amenable to manual therapy techniques such as spinal
manipulation. Scientific evidence to support this tenet, the purported processes
involved, and the manual therapy techniques used, is limited or inconclusive. Yet,
despite this, osteopaths maintain their position that the balance of the ANS is
significant to health, and that manual therapeutic techniques to address ANS
imbalance are appropriate and effective.

18

The Autonomic Nervous System

Introduction
The autonomic nervous system (ANS) is distributed throughout the central and
peripheral nervous systems (Figure 1). The ANS exerts continuous control over
cardiac muscle, smooth muscle, glandular function, and temperature regulation. In
conjunction with the respiratory and endocrine systems, the ANS brings about fine
internal adjustments necessary for homeostasis.

Central Nervous
System

Peripheral
Nervous System

Sensory

Motor

Autonomic
Nervous System
(Involuntary)

Sympathetic
division

Figure 1

Somatic Nervous
System
(Voluntary)

Parasympathetic
division

Organisation of the Nervous System.

Adapted from Marieb (2001).

Anatomy and physiology texts differentiate the sympathetic and parasympathetic

divisions of the ANS by anatomical, physiological, and neurotransmitter differences.
These divisions are thought to function in concert, and are described in undergraduate
texts as having opposite and antagonistic actions. Physiological effects of the
sympathetic system are generally simplified as being arousing and are commonly
described as the fight, flight, or fright responses. In contrast, the parasympathetic
system has been described as rest and digest, as it promotes conservation of energy
and regulates digestion. A third division, the enteric nervous system, regulates
19

sequential action of the gastrointestinal tract, although physiologists often consider

this system separate as it is mostly governed by parasympathetic and sympathetic
activity.

Texts describe both divisions of the ANS as displaying segmental organisation in the
innervation of the body (Figure 2). In the sympathetic nervous system, fibres exit the
spinal cord between the first thoracic and second lumbar vertebra. The fibres then
pass to the sympathetic trunk ganglia flanking these vertebrae and follow one of three
courses: synapse immediately at the same level; travel within the sympathetic trunk to
synapse at a higher or lower level; or pass through the sympathetic trunk to synapse
with prevertebral ganglia. In contrast, the parasympathetic nervous system has a more
restricted distribution. Fibres originate from cell bodies within the brainstem and the
second to fourth sacral segments of the spinal cord to synapse close to the target
organ. The vagus nerve in particular is central to regulation of visceral organs as
numerous vagal branches provide much of the parasympathetic innervation of
thoracic and abdominal organs.

Sympathetic

Parasympathetic

CN III

Eye

CN VII

Lacrimal & salivary glands

CN IX

Eye

CN X
Heart
Lungs

T1

Parotid gland
Heart
Lungs
Upper gastrointestinal tract

Adrenal medulla

Upper gastrointestinal tract

Genitourinary tract
Genitalia
L1

S2 S4

Figure 2

Lower gastrointestinal tract

Genitalia

Structure of the Autonomic Nervous System.

Adapted from Snell (2001).

20

To maintain homeostasis, the ANS detects and responds to a variety of stimuli in the
internal and external environment. This activity results in continual moment-tomoment responses and is commonly thought to be regulated by higher centre control
and peripheral reflex arcs. Yet, as Janig and McLachlan (1992; 1999) observe, the
diversity of the ANS is not limited to a simple neuroendocrine role, as discrete
functional pathways and differentiation of reflex patterns have been identified at
molecular, cellular, and integrative levels. The complex neuroendocrine role of the
ANS is reflected in specialisation of the vagus nerve of the parasympathetic system.
Berthoud and Neuhuber (2000) describe the vagus as having a peripheral and central
interface: mechanical, chemical, and temperature receptors are found in and around
organs, and the vagus also projects to the brainstem and forebrain. Berthoud and
Neuhuber go on to discuss evidence regarding a vagal role in pain perception, in both
a sensory and affective capacity, and that the anatomical connections of the vagus
imply a potential for vagal signals to affect the entire organism.

Autonomic control of viscera is widely regarded as encompassing alteration in blood

flow, blood glucose, motility, and secretions. Under stable environmental conditions,
the regulation of visceral function occurs automatically at the organ level, without
involvement of higher centres. The integration of visceral function frequently
involves higher centres, and is reflected in the precise adaptation of certain organs to
behavioural requirements, for example, bladder and bowel control and social context.
These intricate processes are closely related to the nervous system, the endocrine
system, autonomic reflexes, visceral sensations, emotion generation, and higher centre
function (Janig & Habler, 1995).

In the cardiovascular system, the ANS is essential to cardiovascular control

mechanisms, such as beat-by-beat fluctuations in heart rate and blood pressure. The
sinoatrial (SA) node, which is the main determinate of heart rate, is richly innervated
with sympathetic and parasympathetic fibres. Arousal states such as fear and
excitement increase sympathetic activity to the SA node elevating heart rate and force
of contraction. Sympathetic arousal also stimulates release of the hormones
adrenaline and noradrenalin, and activation of the renin-angiotensin-aldosterone
system of the kidney. These mechanisms act to alter blood pressure and sequester
blood away from areas less vital when faced with threat (e.g. digestive organs).
21

Parasympathetic activity to the heart, mediated by the vagus nerve, produces states of
relaxation and calm. Increased vagal activity to the sinoatrial node reduces heart rate
and blood pressure, increases the beat-to-beat variability of the heart, and reduces
force of contraction. Vagal governance of respiration also modulates cardiovascular
function via respiratory depth and frequency (Task Force of the European Society of
Cardiology and the North American Society of Pacing and Electrophysiology, 1996).
Vagal activity therefore regulates cardiovascular function through a direct contact
with the SA node, and modulates heart rate and blood pressure through respiration
(Stauss, 2003).

Failure or imbalance of the cardiac autonomic mechanisms is widely recognised to

promote life-threatening cardiovascular events. Complex phenomena such as
ventricular tachyarrhythmias and sudden cardiac death are the leading causes of
cardiovascular mortality and are associated with increased sympathetic and decreased
vagal tone. In people with prior cardiac injury, increased sympathetic and decreased
vagal activity can significantly modulate the activity of cardiac pacemaker and
conduction tissue, and unfavourably alter haemodynamics (Sztajzel, 2004; Zhong,
Jan, Ju, & Chon, 2006).

Influences on autonomic function

The ANS is widely accepted to be influenced by numerous extrinsic and intrinsic
factors, which can produce local or generalised effects. Extrinsic stimuli affecting the
ANS range from physical exercise, postural change, extremes of temperature (heat
and cold), pain, and mental stress. These stimuli can cause changes to blood flow and
heart rate, and activation of hormones such as adrenaline and cortisol. Appraisal of
danger, evident in the so-called fight, flight or fright response, is observed to have an
immediate influence on the ANS heart rate and blood pressure increase virtually
instantaneously and are accompanied by sweating and pupillary dilation (Brooks,
Koizumi, & Sato, 1979).

22

Numerous intrinsic factors, such as circadian rhythms and metabolic products, are
recognised to have a widespread influence on the ANS. Extensive and often
detrimental influences on the ANS are associated with many pathologies, such as
endocrine, renal, and neurological disorders (Mathias & Bannister, 1999).
Widespread effects on the ANS are also linked with aging (Docherty, 2002) and in
consumption of chemical agents such as pharmaceuticals, alcohol, and recreational
drugs (Brooks et al., 1979).

Although much knowledge regarding the ANS has unfolded in the last century, many
questions still remain. Berthoud and Neuhuber (2000) comment that the mechanisms
behind central regulation of ANS outflow patterns requires further exploration.
Within the manual therapy professions, questions have predominately focused on
whether autonomic activity is influenced by the mechanical stimulation provided by
manual therapy techniques.

Indicators of autonomic function

Literature indicates that a variety of measures may be used to quantify changes in
autonomic function. These include pupillary diameter (Briggs & Boone, 1988), speed
of pupillary reflex (Gibbons, Gosling, & Holmes, 2000), skin sympathetic nerve
activity (Ray & Monahan, 2002), muscle sympathetic nerve activity (Hume & Ray,
1999), distal skin temperature (Harris & Wagnon, 1987), skin conductance (Chiu &
Wright, 1996; Petersen, Vicenzino, & Wright, 1993), plasma and salivary
concentration of hormones and other neurochemicals (Costa, Lavin, Robertson, &
Biaggioni, 1995; Tuchin, 1998), immune system activity (Brennan et al., 1991), and
heart rate and blood pressure (Fujimoto et al., 1999). Although a number of
physiological measures are available to quantify changes in the ANS, most are not
direct measures of autonomic activity.

The status of the ANS can be directly assessed with scintigraphic and cardiovascular
reflex tests. As these types of tests are invasive and not widely available, heart rate
variability (HRV) has emerged as a simple non-invasive technique which evaluates

23

sympathetic and parasympathetic activity at the sinoatrial level (Sztajzel, 2004; Task
Force, 1996).

Heart Rate Variability

Heart rate variability (HRV) measures the variation in heart rate between consecutive
beats (Niskanen, Tarvainen, Ranta-Aho, & Karjalainen, 2004). The R-R interval of
the electrocardiogram (ECG) (Figure 3) denotes the peak of the R-wave as the
reference point to determine the duration between two consecutive beats. The
variability of R-R intervals has been used for many years to evaluate the ANS in short
term experiments in psychology, cardiovascular physiology, and pharmacology
(Berntson et al., 1997).

Variation in the R-R interval represents the subtle regulation of the dynamic
cardiovascular control mechanisms by the ANS. The sympathetic and
parasympathetic activity directed to the sinoatrial node is mostly synchronous with
each cardiac cycle, but can be modulated by central and peripheral oscillators such as
the respiratory centre in the brainstem, or arterial baroreceptors (Task Force, 1996).
The modulations cause a rhythmic fluctuation in sympathetic and parasympathetic
discharge which manifests as short and long-term oscillations in the cardiac
contraction period. Analysis of these oscillations may permit inferences to be made
on the state and function of sympathetic and parasympathetic activity, the central
oscillators, humoral factors, and the sinoatrial node itself (Task Force, 1996).

Figure 3

Normal Electrocardiogram Waveform

("Electrocardiogram (ECG)," 2006).

24

The clinical utility of HRV is reflected in numerous published works on HRV in the
context of cardiovascular physiology and medicine (Berntson et al., 1997). Reduced
HRV is strongly associated with adverse outcomes (Dekker et al., 2000; Dekker et al.,
1997; Liao et al., 1997; Tsuji et al., 1996), and HRV data has demonstrated that
sympathetic activity is elevated in heart failure and coronary artery disease, and plays
a role in hypertension (Eisenhofer et al., 1996; Huikuri et al., 1996; McCance,
Thompson, & Forfar, 1993). Reduced HRV has been shown to be of prognostic
relevance in progressive heart failure and is associated with increased mortality after
acute myocardial infarction (La Rovere, Bigger, Marcus, Mortara, & Schwartz, 1998;
La Rovere et al., 2003; Ponikowski et al., 1997). Consequently, the most common
clinical application of HRV is predicting risk of death in patients with cardiac disease
(Bigger et al., 1995).

The promise showed by HRV as an easy-to-use marker of cardiac autonomic activity

increased its popularity of use. However, the significance and complexity of HRV
was not widely appreciated or understood prior to the mid-1990s. Consequently, the
Task Force by European Society of Cardiology and the North American Society of
Pacing and Electrophysiology was formed. The Task Force standardised methods of
measurement, nomenclature, definitions, and described clinical applications of HRV
(Task Force, 1996).

Influences on heart rate variability

To better understand the multiple influences on HRV and cardiovascular physiology,
clinicians and investigators have drawn on non-linear dynamics or chaos theory.
Although the term chaos theory has yet to be formally defined, chaos can be more
easily understood by describing it in terms of its behaviour. Chaos is believed by
theorists to display characteristics of both randomness and periodicity, but is distinct
from both. Put simply, random behaviour is unpredictable and never repeats itself,
whereas periodic behaviour is predictable and repeats over a finite period of time.
Chaotic behaviour is considered by theorists to appear disorganised (i.e. random) but
is actually periodic (Decroly & Goldbeter, 1982; Goldberger, 1996; Kaplan & Yorke,
1979).

25

Chaos theory has been utilised to understand a variety of different processes. These
range from fluid turbulence (Kaplan & Yorke, 1979) and weather (Lorenz, 1963;
Pool, 1989b), to biological processes such as epidemics (Olsen & Degn, 1985; Pool,
1989a), biochemical reactions (Decroly & Goldbeter, 1982, 1985), and cardiac
behaviour (Goldberger, Findley, Blackburn, & Mandell, 1984; Goldberger, Shabetai,
Bhargava, West, & Mandell, 1984). To illustrate the characteristics of chaotic
behaviour, that is, periodic from one viewpoint yet random from another, Denton,
Diamond, Helfant, Kahn, & Karaqueuzian (1990) offer the following examples: the
average behaviour of a container of gas molecules can be predicted, however the
individual behaviour of a single molecule cannot; likewise, the average heart rate of a
patient can be predicted, however the individual pattern of R-R intervals cannot.

The HRV data from a patient with heart failure shows reduced or restricted variability
of the R-R intervals (Goldberger, 1997; Goldberger, Findley, Blackburn, & Mandell,
1984). Restricted variability is one that is more uniform and periodic, and shows
predictable oscillations in the heart rate. In contrast, the HRV from a healthy heart
demonstrates a variability which is more complex, less uniform, and more irregular.
The complexity of the variation seen in healthy subjects has lead to the suggestion that
a healthy cardiovascular system is one that can generate chaos (Denton et al., 1990).
Research by Goldberger, who draws heavily on chaos theory, has in the past three
decades provided insight into cardiovascular physiology and disease. Goldberger
(1996) has remarked that a healthy heart beat is chaotic and states that This kind of
complex variability, rather than a regular homeostatic steady state, appears to define
the free-running function of many biological systems. A loss of complex variability
in the cardiovascular system is proposed to be a common feature of cardiovascular
disease. Such loss of complexity, that is, a more predictable and less chaotic state,
means less adaptive capacity in a dynamic environment (Goldberger, 1997;
Kobayashi & Musha, 1982; Lipsitz & Goldberger, 1992; Peng et al., 1993).

The complexity of the cardiovascular system is reflected in the linear and non-linear
influences in its environment. Many of the same extrinsic and intrinsic factors that
influence the ANS also influence HRV. Extrinsic factors include posture (Montano et
al., 1994), exercise (Pober, Braun, & Freedson, 2004; Uusitalo, Laitinen, Vaisanen,
26

Lansimies, & Rauramaa, 2004), mental stress and physical stress (Delaney & Brodie,
2000; Terkelsen, Andersen, Molgaard, Hansen, & Jensen, 2004). Intrinsic factors
include respiratory sinus arrhythmia (Yasuma & Hayano, 2004), sleep processes
(Viola et al., 2002), temperature and neuroendocrine regulation (Task Force, 1996),
and circadian rhythms (Bonnemeier et al., 2003; Molgaard, Sorensen, & Bjerregaard,
1991; Scheer, Van Doornen, & Buijs, 2004).

Gender-related differences in HRV have not been widely investigated and

observations appear dependent on several factors, including age (Bonnemeier et al.,
2003; Jensen-Urstad et al., 1997). Ageing has been observed to alter HRV
extensively, as autonomic regulation becomes attenuated and hormonal and
thermoregulatory rhythms lose strength (Vigo, Guinjoan, Scaramal, Siri, & Cardinali,
2005). Furthermore, these effects are compounded by the generalised effects of
diminished arterial compliance, blunted baroreceptor sensitivity, and aging of cardiac
pacemaker cells. The loss of regulatory components associated with aging leads to a
loss of complexity. The loss of complexity, manifest as restricted or reduced HRV,
impairs the ability to adapt to physiological challenges and promotes greater
cardiovascular risk (Iyengar, Peng, Morin, Goldberger, & Lipsitz, 1996; Korkushko,
Shatilo, Plachinda Yu, & Shatilo, 1991; Yamanaka & Honma, 2006).

Chemical agents that modulate the ANS also influence HRV, including certain
medicines, caffeine, tobacco, and alcohol (Kupari, Virolainen, Koskinen, & Tikkanen,
1993; Task Force, 1996). Smoking (Hayano et al., 1990) and alcohol consumption
(Kupari & Koskinen, 1993) are related to impaired autonomic function, which can
affect HRV. However, lifestyle factors such as these also show gender (JensenUrstad, Jensen-Urstad, Ericson, & Johansson, 1998) and personality (Kamada,
Miyake, Kumashiro, Monou, & Inoue, 1992) variation.

Pathologies such as chronic renal failure (Cloarec-Blanchard, Girard, Houhou,

Grunfeld, & Elghozi, 1992), diabetes (Ewing, Borsey, Bellavere, & Clarke, 1981),
and neurological disorders (Korpelainen, Sotaniemi, Huikuri, & Myllya, 1996) can
also influence HRV. The hypothalamic-pituitary-adrenal (HPA) axis is generally
regarded as a complex neuroendocrine system, which influences and regulates
processes such as digestion, immunity, stress reactions, and mood. Dysregulation of
27

the HPA axis has been associated with alcoholism (Adinoff, Iranmanesh, Veldhuis, &
Fisher, 1998; Thayer, Hall, Sollers, & Fischer, 2006), and impairment of the HPA
axis in heavy drinkers appears to lower HRV (Thayer et al., 2006). Dysregulation of
the HPA axis is also linked with epilepsy (Zobel et al., 2004) and disorders such as
depression, schizophrenia, and anxiety (Drevets, 1999; Thayer & Friedman, 2002).
An impaired HPA axis from affective disorders such as these can also alter cardiac
autonomic tone (Bar et al., 2004; Cohen & Benjamin, 2006; Udupa et al., 2007).

An increase in body weight, by as little as 10%, can influence HRV by reducing

parasympathetic function (Hirsch, Leibel, Mackintosh, & Aguirre, 1991; Hirsch,
Mackintosh, & Leibel, 1991). The same investigators suggest that the reduction in
parasympathetic function may be one of the mechanisms underlying cardiac
alterations (such as arrhythmias) that are often observed in obesity. Elevated insulin
associated with obesity and diabetes is widely recognised as a risk factor for
cardiovascular disease. Yet, evidence regarding the role of elevated insulin in
changes to cardiac autonomic function is conflicting; for example, high insulin levels
seem to trigger sympathetic activation (Tack et al., 1998; Vollenweider et al., 1993),
but increased sympathetic activity has been shown to directly induce insulin
resistance (Flanagan et al., 1999).

Measurement and parameters of heart rate variability

Quantifying cardiac autonomic activity can be done using time and frequency
domains or non-linear methods (Stein & Kleiger, 1999). One of the most widely used
frequency domain analyses is power spectral density (PSD). Power spectral density is
a non-invasive linear method that extracts periodic oscillations from HRV data. The
oscillations are then expressed as a function of frequency and the amplitude quantified
by assessing the area (or PSD) under the curve within each frequency band (Sztajzel,
2004; Zhong, Jan, Ju, & Chon, 2006).

The popularity of PSD stems from the computational ease provided by the nonparametric Fast Fourier Transform. Auto-regressive parametric methods are also used
for PSD but tend to be more complex and the suitability of the chosen model requires

28

verification (Sztajzel, 2004; Zhong et al., 2006). The power spectrum of HRV is
routinely classified into four frequency bands (Task Force, 1996):
1. ultra-low frequency (ULF) (0.0033-0.05 Hz)
2. very low frequency (VLF) (0.003-0.04 Hz)
3. low frequency (LF) (0.04-0.15 Hz)
4. high frequency (HF) (0.15-0.4 Hz).
The boundaries between frequencies are not fixed and may vary with changes to the
autonomic control of the heart. Therefore the ranges defined represent a pragmatic
delineation rather than a functional basis (Sztajzel, 2004; Task Force, 1996).

Each frequency band is associated with a variety of influences on HRV. In order to

extract the signal, the low oscillation of ultra-low frequency requires longer-term
HRV recordings (>20 minutes). The circadian rhythm is the most prominent
oscillation in the ULF band, a major component of which is the diurnal fluctuation of
ANS activity (Buijs, van Eden, Goncharuk, & Kalsbeek, 2003; Stauss, 2003; Sztajzel,
2004). The ANS circadian rhythm is generated by fluctuations within the
hypothalamus, which also influences ULF via other circadian rhythms such as
metabolic and behavioural (Bartness, Song, & Demas, 2001; Stauss, 2003)

The remaining frequency bands can be extracted with shorter-term HRV recordings.
Thermoregulation has been suggested as the primary influence on VLF, although
diverse stimuli and conditions have also been found to contribute. These include
haemorrhage, acidosis, alkalosis, high altitude, posture, congestive heart failure,
breathing patterns, and spinal reflexes (Stauss, 2003). While the determinants of the
VLF and ULF bands is not as well known as the other bands, these components are
thought to account for as much as 95% of 24-hour total power (Pikkujamsa, 1999).

The low frequency band has previously been proposed as an index of pure
sympathetic activity. Recent studies suggest that LF is mediated by both sympathetic
and parasympathetic traffic (Stauss, 2003; Sztajzel, 2004; Task Force, 1996; Zhong et
al., 2006). Baroreceptor activity is thought by some to be the predominant influence
on LF (Sleight et al., 1995), although some human (Cooley et al., 1998) and animal
data (Montano et al., 1996) suggests a medullary origin. Since LF is not specific for

29

either ANS division it is usually not considered a general index of sympathetic

cardiac control or sympatho-vagal balance (Task Force, 1996).

By comparison, the high frequency band is dominated by parasympathetic (vagal)

activity (Stauss, 2003; Task Force, 1996). As vagal governance of respiration
mediates HF, the HF band is also described as the respiratory frequency.
Respiratory-driven vagal modulation of heart rate is termed respiratory sinus
arrhythmia (RSA), which represents spontaneous fluctuations resulting from central
coupling between respiratory oscillators in the brainstem and autonomic outflow
(Stauss, 2003; Sztajzel, 2004). During inspiration this coupling manifests as inhibited
vagal activity, causing the balance of ANS cardiac activity to tip in favour of the
sympathetic system and thus increase heart rate. Correspondingly, expiration releases
the inhibition of vagal activity and heart rate decreases (Stauss, 2003; Sztajzel, 2004).
The frequency and amplitude of the respiratory-driven cardiac fluctuation is also
dependant on respiratory rate and depth.

To summarise, research literature clearly indicates that parasympathetic activity is the

greatest determinant of all HRV (Akselrod et al., 1981; Pagani et al., 1991; Task
Force, 1996; Taylor, Carr, Myers, & Eckberg, 1998). However, intrinsic rhythms
such as thermoregulation and extrinsic factors such as posture must be included as
part determinants of HRV.

Limitations of heart rate variability as an indicator of ANS activity

Heart rate variability data is not a direct measure of cardiac autonomic activity.
Consequently, a potential exists for incorrect conclusions and unfounded
extrapolations when interpreting HRV data and deriving inferences regarding the state
and function of the ANS based on such data (Berntson et al., 1997; Mookherjee,
2003; Niskanen et al., 2004). Furthermore, analysis of HRV is a rapidly evolving
field and there is disagreement regarding quantitative approaches to HRV
measurement due to the multiple and often overlapping non-linear influences (Belova,
Mihaylov, & Piryova, 2007; M. Brennan, Palaniswami, & Kamen, 2001; Guzzetti et

30

al., 2005; Malpas, 2002; Radespiel-Troger, Rauh, Mahlke, Gottschalk, & MuckWeymann, 2003).

The Task Force (1996) points out that measurement, analysis, and interpretation of
HRV has clear pitfalls and caveats that need to be considered by researchers and
clinicians utilising these methods. Research literature is equivocal regarding the most
accurate HRV parameter for clinical use, underpinned by the need for clear
elucidation of the putative link between reduced HRV and mortality (Sztajzel, 2004).
Large intra-individual variation in autonomic function, such as age, gender,
pharmacological agents, psychology, and concomitant disease are also recognised as
factors that prevent prescription of a standardised method of HRV assessment (AbdelRahman, Merrill, & Wooles, 1994; Huikuri et al., 1990; Kupari, Virolainen,
Koskinen, & Tikkanen, 1993).

A further limitation is that stability over time of short-term HRV recordings has
shown variable reliability (Kleiger et al., 1991; Sandercock, Bromley, & Brodie,
2005; Tarkiainen et al., 2005). Coefficients of variation have ranged from <1% to
>100%, and with the absence of Task Force recommendations, targets for acceptable
levels of reliability (4-30%) have been adopted by various investigators on an
apparently arbitrary basis. Despite the wide range of reliability described in the
literature, satisfactory intra-individual reproducibility of 24-hour recordings has been
demonstrated in both healthy populations and those with known heart disease
(Huikuri et al., 1990; Kleiger et al., 1991). With the issues surrounding the stability
of HRV data, the Task Force has recommended that, for clinical purposes, HRV
should only be used to warn of early diabetic neuropathy and predict risk of death
after acute myocardial infarction (AMI).

Heart rate variability has also shown modest or limited sensitivity, specificity, and
positive predictive accuracy in cardiovascular disease. The Task Force has advised
that predictive relationships based on HRV can be degraded by cardiac or neural
abnormalities, autonomic interactions, and respiratory parameter variability.
Moreover, artifact and ectopic beats during HRV recording can considerably interfere
with estimates and may invalidate the measurement or lead to over-editing of raw data
(Pikkujamsa, 1999). The differences in diagnostic odds of HRV between recent and
31

previous literature may reflect changes to early treatment protocols of post-AMI

patients. Or, in high-risk patients, the evidence could suggest that by itself HRV is
insufficient as a risk stratifier (Stein & Kleiger, 1999; Sztajzel, 2004). Consequently,
the limitations of HRV have prompted some authors to reiterate that HRV only
reflects fluctuation in cardiac autonomic input and does not represent mean autonomic
tone (Malik & Camm, 1993; Parati, Mancia, Di Rienzo, & Castiglioni, 2006).

The limitation of multiple and overlapping influences on HRV can complicate

controlling for extraneous variables in experiments. In some studies employing HRV
to evaluate the autonomic effects of manual therapy techniques, results may have
been confounded by other influences; for example, vestibular stimulation (Budgell &
Hirano, 2001) or differences in the application of the technique between practitioners
(Zhang et al., 2006). In another investigation, Cooper (2006) applied two innocuous
non-spinal techniques and two innocuous spinal techniques to subjects across a single
80 minute data collection period. Cooper also failed to show statistically significant
pre-post intervention changes from application of the four consecutive techniques.
The author suggested that the lack of significant variation in results was partly
influenced by skin stimulation, habituation to subsequent stimuli, and psychological
and physiological variation. Recently, Grimm, Cunningham, and Burke (2005)
evaluated differences in autonomic function between healthy and injured subjects.
Although Grimm observed significant differences in skin conductance and
baroreceptor sensitivity, no difference was found in the low and high frequency R-R
interval variables of the injured subjects. These results may have been due to
variables associated with heterogeneity of tissue damage between subjects, and
natural intra-individual variation in ANS indices from hormonal or genetic
differences.

32

Pain
Introduction
Pain has been defined as An unpleasant sensory and emotional experience associated
with actual or potential tissue damage, or described in terms of such damage
(Merskey & Bogduk, 1994, p.210). One component of pain5 is nocioception, which
describes the physiological signal that occurs from stimulation of free nerve endings
(nocioceptors) by stimuli considered capable of causing tissue damage (Siddall &
Cousins, 1997). But, as Melzack and Wall (1965) state, the experience of pain and
nocioception are not one and the same. Pain is considered to involve higher centres
associated with cognition, emotion, and sensation, and that actual or potential tissue
damage stimulates feedback circuits that result in behavioural and autonomic
responses. Although clinical pain management can be hobbled by the mind-body
dichotomy, greater knowledge of the affective-emotional dimension of pain has lead
to better understanding of chronic pain, coping strategies, and effective interventions.

Physiological or sensory dimension of pain

The physiology of pain involves activation of nocioceptors and the relay of stimuli to
the brain where it is recognised as potentially harmful (Siddall & Cousins, 1997).
More commonly, however, insults to the body injure a variety of tissues and produce
inflammation. Tissue damage and inflammation cause a cascade of events to occur
such as lowered threshold of sensory neuron activation, increased rate of firing, and
increased responsiveness to thermal stimuli (Siddall & Cousins, 1997). Concurrently,
inflammatory mediators cause silent sensory fibres, which are usually non-responsive
under normal conditions, to react to mechanical pressure (Siddall & Cousins, 1997).
The term given to the outcome of this process is peripheral sensitisation. Peripheral
sensitisation allows a low-intensity stimulus within the injured area to be perceived as
painful (Butler, 2000; Siddall & Cousins, 1997). The clinical correlate of peripheral
sensitisation is primary hyperalgesia, which is heightened responsiveness to a painful
stimulus within the injured area (Graven-Nielsen & Mense, 2001). If nocioception is
5

Components of pain: nocioception (stimulation of free nerve endings from noxious or tissue damaging stimulus), pain
perception (i.e. cognitive or sensory awareness of pain), pain behaviours such as wincing that are observable behavioural
responses, and personal suffering which is the emotional reaction to pain (Loeser & Melzack, 1999; Merskey & Bogduk, 1994).

33

prolonged, gene induction in the dorsal root ganglia and the dorsal horn of the spinal
cord occurs. This may result in central sensitisation, a term that describes longer-term
alteration in sensory nerve responsiveness, the development of cellular memory for
pain, and the development of connections with nerves that conduct mechanical stimuli
(Siddall & Cousins, 1997). Central sensitisation causes heightened sensitivity of
sensory neurons in a wider area by contributing to the phenomena of allodynia6 and
secondary hyperalgesia7 (Butler, 2000; Siddall & Cousins, 1997).

Affective or emotional dimension of pain

Many factors are believed to account for the affective-emotional dimension of pain.
Subject gender (Keogh, Hatton, & Ellery, 2000), experimenter gender (Aslaksen,
Myrbakk, Hoifodt, & Flaten, 2007; Levine & De Simone, 1991), negative affect
(Rhudy & Meagher, 2003), and fear (Bradley, Silakowski, & Lang, 2008) all
modulate evaluation of pain and subsequent coping strategies.

Attentional bias is a term used in psychology and pain literature which refers to the
tendency toward a particular cognitive strategy to cope with pain. Attentional biases
include ignoring, distraction, catastrophising, positive appraisal, reinterpretation, and
praying (Boothby, Thorn, Stroud, & Jensen, 1999, pp. 343-359.; Keogh et al., 2000).
Research demonstrates that attentional biases such as distraction, avoidance, or
focused attention, affect the speed and accuracy of noxious stimulus detection and
therefore the perception of pain (Miron, Duncan, & Bushnell, 1989).

Attentional bias also influences the perceived intensity or unpleasantness of the

stimulus (Keogh et al., 2000; Miron et al., 1989). Furthermore, a bias of preferential
attention towards pain is proposed to be an important factor in the development of
vulnerability, which can predispose healthy individuals to react negatively to pain
(Keogh, Ellery, Hunt, & Hannent, 2001). An important component of attentional bias
is fear of pain. Fear of pain and hypervigilance are thought to predispose individuals
to chronicity, distress, disability, and greater use of healthcare resources (Keogh et al.,

Allodynia: Pain due to a stimulus which does not normally provoke pain (Merskey & Bogduk, 1994, p. 210)
Hyperalgesia: An increased response to a stimulus which is normally painful (Merskey & Bogduk, 1994, p. 211). Secondary
hyperalgesia is heightened responsiveness of the surrounding uninjured tissue (Butler, 2000).

34

2001; Vlaeyen & Crombez, 1999). In chronic musculoskeletal pain this postulate is
known as the fear-avoidance model (Asmundson & Hadjistavropoulos, 2007) or
fear of (re)injury model (Vlaeyen & Linton, 2000).

Threat value is an important factor in pain as perceived threat demands attention and
higher centre resources (Crombez, Baeyens, Vansteenwegen, & Eelen, 1997;
Moseley, Brhyn, Ilowiecki, Solstad, & Hodges, 2003). Threat value is highly
subjective, and intrinsically linked to fear of pain, attentional bias, control, and
context (Moseley et al., 2003; Munafo & Stevenson, 2003; Vlaeyen & Linton, 2000).
The situational context and meaning ascribed to pain has been shown to have a
particularly significant influence on threat value (Bayer, Baer, & Early, 1991; Smith,
Gracely, & Safer, 1998). To illustrate, Moseley (2003) uses the example that a
professional violinist with a minor finger injury will experience greater pain as the
damage is overlaid with a threat to livelihood and identity. In a person whose
livelihood is not dependant on a high level of finger function, the same minor finger
injury may be experienced as less threatening, and therefore less painful.

A further element associated with threat is that of predictability. Rhudy & Meagher
(2000) have proposed that the possibility of shock induces anxiety, whereas
predictable yet unavoidable shock induces fear. These two emotions have differing
effects on pain. Fear appears to evoke a phenomenon known as stress-induced
analgesia where pain is attenuated by release of endogenous opioids (Rhudy &
Meagher, 2000). Anxiety, a future-oriented emotion, results in apprehensive
anticipation of potential threat which leads to increased environmental and somatic
(body) scanning. The anxiety state can therefore facilitate increased sensory
receptivity and enhance pain (Rhudy & Meagher, 2000). Furthermore, the
anticipation of threat in the absence of actual exposure is enough to potentiate startle
reflexes and autonomic responses (Bradley et al., 2008).

The autonomic nervous system and pain

In broad terms, the ANS response to noxious, tissue-damaging events may be
classified as being specific or generalised. Reactions to pain and injury are widely

35

recognised to include heart rate changes, sweating, and raised serum and salivary
cortisol levels. When confronted with actual or potential damage, the ANS activates
higher centres to co-ordinate strategies and patterns of defence behaviour (Butler,
2000). In a review on pain and autonomic reactions, Benarroch (2001) outlines that
these higher centre mechanisms are invoked via direct projections from the dorsal
horn of the spinal cord to the brainstem, and provide the basis of autonomic,
endocrine, and behavioural responses. The responses include anti-nocioceptive
mechanisms such as cardio-respiratory and renal system changes, analgesia which is
independent of endogenous opioids, and motivational modulation of pain (Benarroch,
2001).

In the periphery, sympathetic neurotransmitters can maintain and enhance

nocioception by augmenting chemical mediators and growth factors (Butler, 2000).
Also observed to occur in the periphery is coupling between sensory and sympathetic
fibres. This coupling has been observed in the sympathetic chain ganglia, and
between sensory nerves and sympathetic nerves traversing or synapsing within the
dorsal root ganglia before entering the spinal cord. The complex interaction between
sensory and sympathetic fibres has been shown to modulate activity in the dorsal root
ganglia (Siddall & Cousins, 1997). This interaction has prompted some to postulate
that changes associated with a phenomenon such as central sensitisation may mean
that activity in sympathetic fibres could lead to abnormal responsiveness of sensory
fibres (Koltzenburg & McMahon, 1991).

Despite the postulated sympathetic contribution to pain, there is evidence to challenge

sympathetic involvement. Schott (1994; 1999) summarises research reporting a lack
of correlation between clinical features of pain and known sympathetic effects, such
as skin temperature and moisture changes. Furthermore, while direct damage to the
sympathetic nervous system is believed to cause pain, it appears that pathological
lesions and stimulation of sympathetic nerves only occasionally cause pain (Schott,
1999). Pain associated with lesions involving sympathetic fibres, such as tumours,
vascular disease, and trauma, has therefore been speculated to be associated with
visceral sensory nerves travelling with the sympathetic nerves, and not the
sympathetic nerves themselves (Schott, 1999).

36

Delayed onset muscle soreness

Delayed onset muscle soreness (DOMS) is the sensation of dull aching pain and
discomfort felt after unaccustomed or strenuous exercise (Croisier et al., 2003; Friden
& Lieber, 2001). The soreness peaks approximately 24-48 hours following exercise,
is accompanied by stiffness, weakness, and tenderness, and disappears completely
within 3-7 days of the precipitating activity (Armstrong, 1984; Graven-Nielsen &
Arendt-Nielsen, 2003). Delayed onset muscle soreness is distinguished from
temporary soreness, which is moderate pain felt during the final stages of fatiguing
exercise and believed to be caused by metabolic waste (Croisier et al., 2003).

Clinical studies have found that the most effective way to induce DOMS is with
eccentric exercise. During eccentric exercise the contracting muscle is forcibly
lengthened, placing high tension on muscle fibres and connective tissue (Proske &
Morgan, 2001). The disruption to skeletal muscle from unaccustomed exercise is not
considered permanent and is not associated with disruption to articular, vascular,
neurological, or osseous structures (Friden, 2002; Proske & Morgan, 2001).

Physiology of delayed onset muscle soreness

The mechanisms underlying DOMS are not completely understood. Earlier theories
included spastic contracture of the muscle (De Vries, 1966), structural damage to the
muscle fibres and connective tissue (Armstrong, 1984), and a loss of calcium
homeostasis in the injured fibre (Armstrong, 1990). The most recent and best
supported hypothesis is mechanical stress triggering structural damage and a
subsequent inflammatory response (Lieber & Friden, 2002).

Described in temporal terms, unaccustomed or strenuous exercise causes microdamage to muscle fibres but no soreness immediately after exercise. The mechanical
disruption disturbs the chemical milieu of muscle which is proposed to trigger a
subsequent inflammatory response. The inflammatory response develops over several
hours, and inflammatory mediators such as bradykinin are believed to stimulate free
nerve endings and sensitise them so as to respond to normal innocuous stimuli (also
known as peripheral sensitisation) (Mense & Meyer, 1988; Proske & Morgan, 2001).

37

On microscopy of muscle tissue taken at biopsy, there is direct evidence of muscle

damage such as disruption to muscle fibres and regional disorganisation of filaments
(Proske & Morgan, 2001; Yu, Carlsson, & Thornell, 2004). Structural damage is also
reflected in objective tests of the mechanical properties of muscle: DOMS is
associated with decreased active tension, increased passive tension, altered muscle
length (shorter), and reduced range of motion (Friden & Lieber, 2001). Changes in
serum and urine constituents also indicate increased permeability or breakdown of the
muscle cell membrane, increased cell disruption, and collagen and myosin turnover
(Blais, Adam, Massicotte, & Peronnet, 1999).

There is some debate within the literature regarding the proposed mechanisms
involved in DOMS. Inflammation subsequent to damage is not always confirmed
(Malm et al., 2000; Nosaka, Newton, & Sacco, 2002; Vincent & Vincent, 1997) and
the muscle damage theory has too been challenged (Friden & Lieber, 2001; Newham,
1988). Blaise et al. (1999) contend that while some inflammatory mediators are
known to stimulate nocioceptors, the involvement of many of these substances in
DOMS remains largely hypothetical.

Conjecture also surrounds the involvement of connective tissue in the DOMS process.
Graven-Nielsen, Gibson, and Arendt-Nielsen (2006) have recently implicated the role
of fascial tissue in DOMS. Based on subjective reports by research participants, other
investigators have proposed that mechanical damage to the musculotendinous
junction (MTJ) stimulates the dense free nerve endings found at the MTJ and signals
nocioception (Cleak & Eston, 1992). Yet, the nociceptive characteristics of tendon
are not clear (Gibson, Arendt-Nielsen, & Graven-Nielsen, 2006) and other studies
indicate this effect may depend on the amount of damage at the MTJ (Bajaj, GravenNielsen, & Arendt-Nielsen, 2001; Eston, Critchley, & Baltzopoulos, 1994), and how
large the muscle attachment area is (Bajaj et al., 2001; Brand, Beach, & Thompson,
1981).

Some reports propose that central mechanisms may be important in pain associated
with DOMS. Gibson et al. (2006) suggest that central sensitisation may be involved
after finding greater referred pain frequency and enlarged pain areas during DOMS
38

compared to pre-DOMS. Similarly, Bajaj et al. (2001), found correlations between

tenderness at the musculotendinous junction and the sensory and affective
components of the pain-rating index. These findings were backed by the
simultaneous presence of a significant reduction in mean arterial pressure during peak
DOMS, suggesting central mechanisms were involved. Several authors claim that
input from mechanically sensitive muscle spindles and golgi tendon organs interact
with neurons in the spinal cord that also have connections to pain pathways (Barlas,
Walsh, Baxter, & Allen, 2000; Weerakkody, Whitehead, Canny, Gregory, & Proske,
2001). Another related suggestion is that inhibitory neurons in the spinal cord
become excited from DOMS/injury and interact with fibres relaying noxious stimuli.

The theories regarding the involvement of central mechanisms in DOMS parallel

those of autonomic reflexes, as muscle sensory fibres have elicited cardiovascular
changes via spinal cord interactions (Coote & Bothams, 2001; Kerman & Yates,
1999; Sato, Sato, & Schmidt, 1979). Recently, Gladwell et al. (2005) have observed
that muscle fibres responding to mechanical deformation, specifically stretch,
selectively inhibited cardiac vagal tone to produce tachycardia. Therefore muscle
mechanoreceptors could conceivably play a part in the reflex connections that exist to
mediate somato-autonomic activities and in fight or flight responses.

Despite the exact mechanisms being unclear, there is general agreement that DOMS
appears to be beneficial in terms of the objective properties of muscle. Yu et al.
(2004) propose that remodelling as opposed to damage is the mechanism at work,
supported by the so-called repeated-bout effect. The repeated-bout effect occurs
when subsequent bouts of eccentric exercise, from 1-10 weeks after the initial bout,
produce much less muscle damage implying an adaptive and protective function
(Ebbeling & Clarkson, 1989; Golden & Dudley, 1992; Nosaka, Clarkson, McGuiggin,
& Byrne, 1991; Paddon-Jones, Muthalib, & Jenkins, 2000). Even second bouts
performed during the early recovery period (1-5 days) of an initial bout have not
exacerbated muscle damage or retarded the recovery process (Ebbeling & Clarkson,
1989; Paddon-Jones et al., 2000), with some studies showing this effect regardless of
the intensity and volume of eccentric action performed in the second bout (Chen &
Nosaka, 2006). Light eccentric exercise, which does not significantly change markers

39

of muscle damage, is also believed to confer a protective effect (Lavender & Nosaka,
2008).

A combination of neural, cellular and mechanical factors is thought to be responsible

for the repeated bout effect (McHugh, 2003). Connective tissue shows greater
resilience to subsequent provocation, repair mechanisms of contractile tissue show
altered fibre-type composition and protein gene-expression, and motor unit
recruitment patterns better distribute workload (Croisier et al., 2003; Mair et al., 1995;
Nosaka & Clarkson, 1995). The suggestion of adaptation supports the idea that mild
eccentric exercise may have a useful clinical application in prevention of major injury
(Croisier et al., 2003; Friden, 2002; Proske & Morgan, 2001), although it is not
currently known how much muscle damage might be necessary for producing such an
adaptive effect (Lavender & Nosaka, 2008).

Delayed onset muscle soreness as a model of pain

Pain is a complex phenomenon involving peripheral mechanisms and higher centre
involvement (Melzack & Wall, 1965). Delayed onset muscle soreness as a model of
pain in terms of the physiological-sensory dimension, involves micro-damage to
tissue and stimulation of free nerve endings from the breakdown products of tissue
damage. Furthermore, the proposed mechanisms underlying DOMS also include
inflammatory response to such damage. The inflammatory substances implicated,
such as bradykinin, are known to stimulate and sensitise free-nerve endings that relay
information regarding noxious stimuli. As a model of pain in terms of the affective or
emotional dimension of pain, DOMS would, like other noxious stimuli, be dependant
upon aspects such as cognitive appraisal of threat (Jackson et al., 2005; Moseley et al.,
2003), environmental context (Malenbaum, Keefe, Williams, Ulrich, & Somers,
2008), coping strategies (Crombez, Eccleston, De Vlieger, Van Damme, & De Clercq,
2008), and prevailing emotions (e.g. fear or anxiety) (Rhudy & Meagher, 2000).

As the aim of this project was to explore mild to moderate musculoskeletal injury on
the ANS, DOMS was selected as a model of tissue injury that could be induced under
controlled conditions. Compared to naturally occurring injuries, using a DOMS-

40

model would partially control for variability in severity and damage to tissues other
than myofascia. The temporal nature of DOMS was considered useful to compare
subjective appraisal of pain with the sequence of events thought to occur in DOMS.
Since DOMS is not associated with chronicity, and believed to have an adaptive role,
DOMS may be considered an ethically appropriate model of pain to use in
experimental research.

41

Summary and aims of research

Osteopaths have historically maintained a central tenet within osteopathic literature,
namely that visceral and musculoskeletal disturbance can affect ANS balance. The
perturbation of the ANS from such disturbance is said to affect structures elsewhere in
the body via common autonomic segments. This concept provides part of the
rationale for treatment approach and therapeutic techniques such as spinal
manipulation. Yet, while ANS changes have been shown to occur in response to
noxious stimuli and with some diseases, studies to date do not support the osteopathic
concept that non-pathological disturbance can perturb the ANS. Furthermore, claims
that osteopathic techniques such as spinal manipulation can address purported ANS
perturbation have not been validated.

The mechanisms underlying spinal manipulation have not been fully elucidated.
There is also limited evidence regarding the other links in the purported causal chain
between visceral and musculoskeletal disturbance and the ANS. Nonetheless, the
primary focus of previous investigations has been the cause-effect relationship
between spinal manipulation and the ANS. Osteopathy has a number of areas to
evaluate, for example: whether mild to moderate musculoskeletal disturbance affects
the ANS; what magnitude of effect spinal manipulation has on the ANS; whether the
direction of such an effect is favourable or not; and the clinical significance of the
techniques. The objective of the investigation documented in Section 2 of this
dissertation was to determine whether a mild musculoskeletal disturbance, such as
that evident in DOMS, has the capability to influence the ANS as measured by heart
rate variability.

42

References
Abdel-Rahman, A. R., Merrill, R. H., & Wooles, W. R. (1994). Gender-related
differences in the baroreceptor reflex control of heart rate in normotensive
humans. J Appl Physiol, 77(2), 606-613.
Adachi, T., Meguro, K., Sato, A., & Sato, Y. (1990). Increases in cerebral blood flow
induced by nociceptive stimulation in ualothane-anesthetizen rats. Pain,
41(Supplement 1), S68.
Adinoff, B., Iranmanesh, A., Veldhuis, J., & Fisher, L. (1998). Disturbances of the
stress response: the role of the HPA axis during alcohol withdrawal and
abstinence. Alcohol Health Res World, 22(1), 67-72.
Akselrod, S., Gordon, D., Ubel, F. A., Shannon, D. C., Berger, A. C., & Cohen, R. J.
(1981). Power spectrum analysis of heart rate fluctuation: a quantitative probe
of beat-to-beat cardiovascular control. Science, 213(4504), 220-222.
Arendt-Nielsen, L., Laursen, R. J., & Drewes, A. M. (2000). Referred pain as an
indicator for neural plasticity. Prog Brain Res, 129, 343-356.
Arendt-Nielsen, L., & Svensson, P. (2001). Referred muscle pain: basic and clinical
findings. Clin J Pain, 17(1), 11-19.
Armstrong, R. B. (1984). Mechanisms of exercise-induced delayed onset muscular
soreness: a brief review. Med Sci Sports Exerc, 16(6), 529-538.
Armstrong, R. B. (1990). Initial events in exercise-induced muscular injury. Med Sci
Sports Exerc, 22(4), 429-435.
Aslaksen, P. M., Myrbakk, I. N., Hoifodt, R. S., & Flaten, M. A. (2007). The effect of
experimenter gender on autonomic and subjective responses to pain stimuli.
Pain, 129(3), 260-268.
Asmundson, G. J., & Hadjistavropoulos, H. D. (2007). Is high fear of pain associated
with attentional biases for pain-related or general threat? A categorical
reanalysis. J Pain, 8(1), 11-18.
Bajaj, P., Graven-Nielsen, T., & Arendt-Nielsen, L. (2001). Post-exercise muscle
soreness after eccentric exercise: psychophysical effects and implications on
mean arterial pressure. Scand J Med Sci Sports, 11(5), 266-273.
Bar, K. J., Greiner, W., Jochum, T., Friedrich, M., Wagner, G., & Sauer, H. (2004).
The influence of major depression and its treatment on heart rate variability
and pupillary light reflex parameters. J Affect Disord, 82(2), 245-252.
Barlas, P., Walsh, D. M., Baxter, G. D., & Allen, J. M. (2000). Delayed onset muscle
soreness: effect of an ischaemic block upon mechanical allodynia in humans.
Pain, 87(2), 221-225.
Bartness, T. J., Song, C. K., & Demas, G. E. (2001). SCN efferents to peripheral
tissues: implications for biological rhythms. J Biol Rhythms, 16(3), 196-204.
Bayer, T. L., Baer, P. E., & Early, C. (1991). Situational and psychophysiological
factors in psychologically induced pain. Pain, 44, 45-50.
Beacham, W. S., & Perl, E. R. (1964). Characteristics of a Spinal Sympathetic Reflex.
J Physiol, 173, 431-448.
Beal, M. C. (1983). Palpatory testing for somatic dysfunction in patients with
cardiovascular disease. J Am Osteopath Assoc, 82(11), 822-831.
Beal, M. C. (1985). Viscerosomatic reflexes: a review. J Am Osteopath Assoc, 85(12),
786-801.

43

Belova, N. Y., Mihaylov, S. V., & Piryova, B. G. (2007). Wavelet transform: A better
approach for the evaluation of instantaneous changes in heart rate variability.
Auton Neurosci, 131(1-2), 107-122.
Benarroch, E. E. (2001). Pain-autonomic interactions: a selective review. Clin Auton
Res, 11(6), 343-349.
Berntson, G. G., Bigger, J. T., Jr., Eckberg, D. L., Grossman, P., Kaufmann, P. G.,
Malik, M., et al. (1997). Heart rate variability: origins, methods, and
interpretive caveats. Psychophysiology, 34(6), 623-648.
Berthoud, H. R., & Neuhuber, W. L. (2000). Functional and chemical anatomy of the
afferent vagal system. Auton Neurosci, 85(1-3), 1-17.
Bielefeldt, K., & Gebhart, G. F. (2006). Visceral pain: basic mechanisms. In S. B.
McMahon & M. Koltzenburg (Eds.), Wall and Melzack's textbook of pain (5th
ed., pp. 721-736.). London: Elsevier.
Bigger, J. T., Jr., Fleiss, J. L., Steinman, R. C., Rolnitzky, L. M., Schneider, W. J., &
Stein, P. K. (1995). RR variability in healthy, middle-aged persons compared
with patients with chronic coronary heart disease or recent acute myocardial
infarction. Circulation, 91(7), 1936-1943.
Blais, J., C., Adam, A., Massicotte, D., & Peronnet, F. (1999). Increase in blood
bradykinin concentration after eccentric weight-training exercise in men. J
Appl Physiol, 87(3), 1197-1201.
Bonica, J. J. (1992). Clinical importance of hyperalgesia. In J. W.D. Willis (Ed.),
Hyperalgesia and allodynia (pp. 17-43.). New York: Raven Press.
Bonnemeier, H., Richardt, G., Potratz, J., Wiegand, U. K., Brandes, A., Kluge, N., et
al. (2003). Circadian profile of cardiac autonomic nervous modulation in
healthy subjects: differing effects of aging and gender on heart rate variability.
J Cardiovasc Electrophysiol, 14(8), 791-799.
Boothby, J. L., Thorn, B. E., Stroud, M. W., & Jensen, M. P. (1999). Coping with
pain. In R. J. Gatchel & D. C. Turk (Eds.), Psychosocial factors in pain.
Edinburgh: Guilford Press.
Bradley, M. M., Silakowski, T., & Lang, P. J. (2008). Fear of pain and defensive
activation. Pain, 137(1), 156-163.
Brand, P. W., Beach, R. B., & Thompson, D. E. (1981). Relative tension and potential
excursion of muscles in the forearm and hand. J Hand Surg [Am], 6(3), 209219.
Brennan, M., Palaniswami, M., & Kamen, P. (2001). Do existing measures of
Poincare plot geometry reflect nonlinear features of heart rate variability?
IEEE Trans Biomed Eng, 48(11), 1342-1347.
Brennan, P. C., Kokjohn, K., Kaltinger, C. J., Lohr, G. E., Glendening, C., &
Hondras, M. A. (1991). Enhanced phagocytic cell respiratory burst induced by
spinal manipulation: potential role of Substance P. J Manipulative Physiol
Ther, 14(7), 399-408.
Briggs, L., & Boone, W. R. (1988). Effects of a chiropractic adjustment on changes in
pupillary diameter: a model for evaluating somatovisceral response. J
Manipulative Physiol Ther, 11(3), 181-189.
Brooks, C. M., Koizumi, K., & Sato, A. (Eds.). (1979). Integrative functions of the
autonomic nervous system. Tokyo: Elsevier / North-Holland Biomedical Press.
Budgell, B., & Hirano, F. (2001). Innocuous mechanical stimulation of the neck and
alterations in heart-rate variability in healthy young adults. Auton Neurosci,
91(1-2), 96-99.

44

Budgell, B., & Polus, B. (2006). The effects of thoracic manipulation on heart rate
variability: a controlled crossover trial. J Manipulative Physiol Ther, 29(8),
603-610.
Buijs, R. M., van Eden, C. G., Goncharuk, V. D., & Kalsbeek, A. (2003). The
biological clock tunes the organs of the body: timing by hormones and the
autonomic nervous system. J Endocrinol, 177(1), 17-26.
Butler, D. S. (2000). The Sensitive Nervous System. Adelaide: NOI Group.
Chen, T. C., & Nosaka, K. (2006). Effects of number of eccentric muscle actions on
first and second bouts of eccentric exercise of the elbow flexors. J Sci Med
Sport, 9, 57-66.
Chiu, T. W., & Wright, A. (1996). To compare the effects of different rates of
application of a cervical mobilisation technique on sympathetic outflow to the
upper limb in normal subjects. Man Ther, 1(4), 198-203.
Cleak, M. J., & Eston, R. G. (1992). Delayed onset muscle soreness: mechanisms and
management. J Sports Sci, 10(4), 325-341.
Cloarec-Blanchard, L., Girard, A., Houhou, S., Grunfeld, J. P., & Elghozi, J. L.
(1992). Spectral analysis of short-term blood pressure and heart rate variability
in uremic patients. Kidney Int Suppl, 37, S14-18.
Cohen, H., & Benjamin, J. (2006). Power spectrum analysis and cardiovascular
morbidity in anxiety disorders. Auton Neurosci, 128(1-2), 1-8.
Cooley, R. L., Montano, N., Cogliati, C., van de Borne, P., Richenbacher, W., Oren,
R., et al. (1998). Evidence for a central origin of the low-frequency oscillation
in RR-interval variability. Circulation, 98(6), 556-561.
Cooper, B. J. (2006). Autonomic effects of innocuous spinal vs innocuous non-spinal
somatic stimulation in the awake human. Unitec New Zealand, Auckland.
Coote, J. H., & Bothams, V. F. (2001). Cardiac vagal control before, during and after
exercise. Exp Physiol, 86(6), 811-815.
Costa, F., Lavin, P., Robertson, D., & Biaggioni, I. (1995). Effect of neurovestibular
stimulation on autonomic regulation. Clin Auton Res, 5, 289-293.
Cox, J. M., Gorbis, S., Dick, L. M., Rogers, J. C., & Rogers, F. J. (1987). Palpable
musculoskeletal findings in coronary artery disease: results of a double-blind
study. J Amer Osteopath Assoc, 82, 832-836.
Croisier, J. L., Camus, G., Forthomme, B., Maquet, D., Vanderthommen, M., &
Crielaard, J. M. (2003). Delayed onset muscle soreness induced by eccentric
isokinetic exercise. Isokinet Exerc Sci, 11(1), 21-29.
Crombez, G., Baeyens, F., Vansteenwegen, D., & Eelen, P. (1997). Startle
intensification during painful heat. Eur J Pain, 1(2), 87-94.
Crombez, G., Eccleston, C., De Vlieger, P., Van Damme, S., & De Clercq, A. (2008).
Is it better to have controlled and lost than never to have controlled at all? An
experimental investigation of control over pain. Pain, 137(3):631-9.
De Vries, H. A. (1966). Quantitative electromyographic investigation of the spasm
theory of muscle pain. Am J Phys Med, 45(3), 119-134.
Decroly, O., & Goldbeter, A. (1982). Birhythmicity, chaos, and other patterns of
temporal self-organization in a multiply regulated biochemical system. Proc
Natl Acad Sci U S A, 79(22), 6917-6921.
Decroly, O., & Goldbeter, A. (1985). Selection between multiple periodic regimes in
a biochemical system: complex dynamic behaviour resolved by use of onedimensional maps. J Theor Biol, 113(4), 649-671.

45

Delaney, J. P., & Brodie, D. A. (2000). Effects of short-term psychological stress on

the time and frequency domains of heart-rate variability. Percept Mot Skills,
91(2), 515-524.
Denton, T. A., Diamond, G. A., Helfant, R. H., Kahn, S., & Karaqueuzian, H. (1990).
Fascinating rhythm: A primer on chaos theory and its application to
cardiology. Am Heart J, 120, 1419-1440.
Dekker, J. M., Crow, R. S., Folsom, A. R., Hannan, P. J., Liao, D., Swenne, C. A., et
al. (2000). Low heart rate variability in a 2-minute rhythm strip predicts risk of
coronary heart disease and mortality from several causes: the ARIC study.
Circulation, 102(11), 1239-1244.
Dekker, J. M., Schouten, E. G., Klootwijk, P., Pool, J., Swenne, C. A., & Kromhout,
D. (1997). Heart rate variability from short electrocardiographic recordings
predicts mortality from all causes in middle-aged and elderly men. The
Zutphen Study. Am J Epidemiol, 145(10), 899-908.
DiGiovanna, E. L., Schiowitz, S., & Dowling, D. J. (Eds.). (2005). An osteopathic
approach to diagnosis and treatment (3rd ed.). Philadelphia: Lippincott,
Williams & Wilkins.
Docherty, J. R. (2002). Age-related changes in adrenergic neuroeffector transmission.
Auton Neurosci, 96(1), 8-12.
Drevets, W. C. (1999). Prefrontal cortical-amygdalar metabolism in major depression.
Ann N Y Acad Sci, 877, 614-637.
Driscoll, M. D., & Hall, M. J. (2000). Effects of spinal manipulative therapy on
autonomic activity and the cardiovascular system: a case study using the
electrocardiogram and arterial tonometry. J Manipulative Physiol Ther, 23(8),
545-550.
Ebbeling, C. B., & Clarkson, P. M. (1989). Exercise-induced muscle damage and
adaptation. Sports Med, 7(4), 207-234.
Eingorn, A. M., & Muhs, G. J. (1999). Rationale for assessing the effects of
manipulative therapy on autonomic tone by analysis of heart rate variability. J
Manipulative Physiol Ther, 22(3), 161-165.
Eisenhofer, G., Friberg, P., Rundqvist, B., Quyyumi, A. A., Lambert, G., Kaye, D.
M., et al. (1996). Cardiac sympathetic nerve function in congestive heart
failure. Circulation, 93(9), 1667-1676.
Electrocardiogram (ECG). (2006). Retrieved 21 April, 2006, from
http://www.cs.wright.edu/~phe/EGR199/Lab_1/
Ernst, E., & Canter, P. H. (2006). A systematic review of systematic reviews of spinal
manipulation. J R Soc Med, 99(4), 192-196.
Eston, R. G., Critchley, N., & Baltzopoulos, V. (1994). Delayed onset soreness,
strength loss characteristics and creatine kinase activity following downhill
running. J Sports Sci, 12(135).
Evans, D. W. (2002). Mechanisms and effects of spinal high-velocity, low-amplitude
thrust manipulation: previous theories. J Manipulative Physiol Ther, 25(4),
251-262.
Ewing, D. J., Borsey, D. Q., Bellavere, F., & Clarke, B. F. (1981). Cardiac autonomic
neuropathy in diabetes: comparison of measures of R-R interval variation.
Diabetologia, 21(1), 18-24.
Flanagan, D. E., Vaile, J. C., Petley, G. W., Moore, V. M., Godsland, I. F.,
Cockington, R. A., et al. (1999). The autonomic control of heart rate and
insulin resistance in young adults. J Clin Endocrinol Metab, 84(4), 1263-1267.

46

Friden, J. (2002). Delayed onset muscle soreness. Scand J Med Sci Sports, 12(6), 327328.
Friden, J., & Lieber, R. L. (2001). Eccentric exercise-induced injuries to contractile
and cytoskeletal muscle fibre components. Acta Physiol Scand, 171(3), 321326.
Fujimoto, T., Budgell, B., Uchida, S., Suzuki, A., & Meguro, K. (1999). Arterial
tonometry in the measurement of the effects of innocuous mechanical
stimulation of the neck on heart rate and blood pressure. J Auton Nerv Syst,
75(2-3), 109-115.
Giamberardino, M. A., Affaitati, G., Lerza, R., & Vecchiet, L. (2000). Pre-emptive
analgesia in rats with artificial ureteric calculosis. Effects on visceral pain
behavior in the post-operative period. Brain Res, 878(1-2), 148-154.
Gibbons, P., & Tehan, P. (2006). Manipulation of the spine, thorax and pelvis: an
osteopathic perspective (2nd ed.). London: Churchill Livingstone.
Gibbons, P. F., Gosling, C. M., & Holmes, M. (2000). Short-term effects of cervical
manipulation on edge light pupil cycle time: a pilot study. J Manipulative
Physiol Ther, 23(7), 465-469.
Gibson, W., Arendt-Nielsen, L., & Graven-Nielsen, T. (2006). Delayed onset muscle
soreness at tendon-bone junction and muscle tissue is associated with
facilitated referred pain. Exp Brain Res, 174(2), 351-360.
Gladwell, V. F., Fletcher, J., Patel, N., Elvidge, L. J., Lloyd, D., Chowdhary, S., et al.
(2005). The influence of small fibre muscle mechanoreceptors on the cardiac
vagus in humans. J Physiol, 567(Pt 2), 713-721.
Glossary of Osteopathic Terminology (Ed.) (2004). The Educational Council on
Osteopathic Principles and the American Association of Colleges of
Osteopathic Medicine.
Goldberger, A. L. (1996). Non-linear dynamics for clinicians: chaos theory, fractals,
and complexity at the bedside. Lancet, 347(9011), 1312-1314.
Goldberger, A. L. (1997). Fractal variability versus pathologic periodicity: complexity
loss and stereotypy in disease. Perspect Biol Med, 40(4), 543-561.
Goldberger, A. L., Findley, L. J., Blackburn, M. R., & Mandell, A. J. (1984).
Nonlinear dynamics in heart failure: implications of long-wavelength
cardiopulmonary oscillations. Am Heart J, 107(3), 612-615.
Goldberger, A. L., Shabetai, R., Bhargava, V., West, B. J., & Mandell, A. J. (1984).
Nonlinear dynamics, electrical alternans, and pericardial tamponade. Am
Heart J, 107(6), 1297-1299.
Golden, C. L., & Dudley, G. A. (1992). Strength after bouts of eccentric or concentric
actions. Med Sci Sports Exerc, 24(8), 926-933.
Graven-Nielsen, T., & Arendt-Nielsen, L. (2003). Induction and assessment of muscle
pain, referred pain, and muscular hyperalgesia. Curr Pain Headache Rep,
7(6), 443-451.
Graven-Nielsen, T., Gibson, W., & Arendt-Nielsen, L. (2006). 326 Fascial
involvement in delayed onset muscle soreness. Eur J Pain, 10(Supplement 1),
S87.
Graven-Nielsen, T., & Mense, S. (2001). The peripheral apparatus of muscle pain:
evidence from animal and human studies. Clin J Pain, 17(1), 2-10.
Grimm, D. R., Cunningham, B. M., & Burke, J. R. (2005). Autonomic nervous
system function among individuals with acute musculoskeletal injury. J
Manipulative Physiol Ther, 28(1), 44-51.

47

Guzzetti, S., Borroni, E., Garbelli, P. E., Ceriani, E., Della Bella, P., Montano, N., et
al. (2005). Symbolic dynamics of heart rate variability: a probe to investigate
cardiac autonomic modulation. Circulation, 112(4), 465-470.
Harris, W., & Wagnon, R. J. (1987). The effects of chiropractic adjustments on distal
skin temperature. J Manipulative Physiol Ther, 10(2), 57-60.
Hayano, J., Yamada, M., Sakakibara, Y., Fujinami, T., Yokoyama, K., Watanabe, Y.,
et al. (1990). Short- and long-term effects of cigarette smoking on heart rate
variability. Am J Cardiol, 65(1), 84-88.
Hirsch, J., Leibel, R. L., Mackintosh, R., & Aguirre, A. (1991). Heart rate variability
as a measure of autonomic function during weight change in humans. Am J
Physiol, 261(6 Pt 2), R1418-1423.
Hirsch, J., Mackintosh, R., & Leibel, R. L. (1991). Nutritionally-induced changes in
parasympathetic function. Brain Res Bull, 27(3-4), 541-542.
Huikuri, H. V., Kessler, K. M., Terracall, E., Castellanos, A., Linnaluoto, M. K., &
Myerburg, R. J. (1990). Reproducibility and circadian rhythm of heart rate
variability in healthy subjects. Am J Cardiol, 65(5), 391-393.
Huikuri, H. V., Ylitalo, A., Pikkujamsa, S. M., Ikaheimo, M. J., Airaksinen, K. E.,
Rantala, A. O., et al. (1996). Heart rate variability in systemic hypertension.
Am J Cardiol, 77(12), 1073-1077.
Hume, K. M., & Ray, C. A. (1999). Sympathetic responses to head-down rotations in
humans. J Appl Physiol, 86(6), 1971-1976.
Iyengar, N., Peng, C. K., Morin, R., Goldberger, A. L., & Lipsitz, L. A. (1996). Agerelated alterations in the fractal scaling of cardiac interbeat interval dynamics.
Am J Physiol, 271(4 Pt 2), R1078-1084.
Jackson, T., Pope, L., Nagasaka, T., Fritch, A., Iezzi, T., & Chen, H. (2005). The
impact of threatening information about pain on coping and pain tolerance. Br
J Health Psychol, 10(Pt 3), 441-451.
Janig, W., & Habler, H.-J. (1995). Visceral-autonomic integration. In G. F. Gebhart
(Ed.), Visceral pain. Progress in pain research and management, Vol. 5.
Seattle: IASP Press.
Janig, W., & McLachlan, E. M. (1992). Characteristics of function-specific pathways
in the sympathetic nervous system. Trends Neurosci, 15(12), 475-481.
Janig, W., & McLachlan, E. M. (1999). Neurobiology of the autonomic nervous
system. In C. J. Mathias & R. Bannister (Eds.), Autonomic failure: a textbook
of clinical disorders of the autonomic nervous system (pp. 3-15.). New York:
Oxford University Press.
Jensen-Urstad, K., Storck, N., Bouvier, F., Ericson, M., Lindblad, L. E., & JensenUrstad, M. (1997). Heart rate variability in healthy subjects is related to age
and gender. Acta Physiol Scand, 160(3), 235-241.
Jensen-Urstad, M., Jensen-Urstad, K., Ericson, M., & Johansson, J. (1998). Heart rate
variability is related to leucocyte count in men and to blood lipoproteins in
women in a healthy population of 35-year-old subjects. J Intern Med, 243(1),
33-40.
Kamada, T., Miyake, S., Kumashiro, M., Monou, H., & Inoue, K. (1992). Power
spectral analysis of heart rate variability in Type As and Type Bs during
mental workload. Psychosom Med, 54(4), 462-470.
Kaplan, J. L., & Yorke, J. A. (1979). The onset of chaos in a fluid flow model of
Lorenz. Ann NY Acad Sci, 316(400-7.).
Karason, A. B., & Drysdale, I. P. (2003). Somatovisceral response following
osteopathic HVLAT: a pilot study on the effect of unilateral lumbosacral high-

48

velocity low-amplitude thrust technique on the cutaneous blood flow in the

lower limb. J Manipulative Physiol Ther, 26(4), 220-225.
Kaufman, A., Sato, A., Sato, Y., & Sugimoto, H. (1977). Reflex changes in heart rate
after mechanical and thermal stimulation of the skin at various segmental
levels in cats. Neuroscience, 2(1), 103-109.
Keogh, E., Ellery, D., Hunt, C., & Hannent, I. (2001). Selective attentional bias for
pain-related stimuli amongst pain fearful individuals. Pain, 91(1-2), 91-100.
Keogh, E., Hatton, K., & Ellery, D. (2000). Avoidance versus focused attention and
the perception of pain: differential effects for men and women. Pain, 85(1-2),
225-230.
Kerman, I. A., & Yates, B. J. (1999). Patterning of somatosympathetic reflexes. Am J
Physiol, 277(3 Pt 2), R716-724.
Kleiger, R. E., Bigger, J. T., Bosner, M. S., Chung, M. K., Cook, J. R., Rolnitzky, L.
M., et al. (1991). Stability over time of variables measuring heart rate
variability in normal subjects. Am J Cardiol, 68(6), 626-630.
Knutson, G. A. (2001). Significant changes in systolic blood pressure post vectored
upper cervical adjustment vs resting control groups: a possible effect of the
cervicosympathetic and/or pressor reflex. J Manipulative Physiol Ther, 24(2),
101-109.
Kobayashi, M., & Musha, T. (1982). 1/f fluctuation of heartbeat period. IEEE Trans
Biomed Eng, 29(6), 456-457.
Koltzenburg, M., & McMahon, S. B. (1991). The enigmatic role of the sympathetic
nervous system in chronic pain. Trends Pharmacol Sci, 12(11), 399-402.
Korkushko, O. V., Shatilo, V. B., Plachinda Yu, I., & Shatilo, T. V. (1991).
Autonomic control of cardiac chronotropic function in man as a function of
age: assessment by power spectral analysis of heart rate variability. J Auton
Nerv Syst, 32(3), 191-198.
Korpelainen, J. T., Sotaniemi, K. A., Huikuri, H. V., & Myllya, V. V. (1996).
Abnormal heart rate variability as a manifestation of autonomic dysfunction in
hemispheric brain infarction. Stroke, 27(11), 2059-2063.
Kuchera, M. L., & Kuchera, W. A. (1993). Osteopathic principles in practice (2nd
ed.). Columbus: Greyden Press.
Kupari, M., & Koskinen, P. (1993). Relation of left ventricular function to habitual
alcohol consumption. Am J Cardiol, 72(18), 1418-1424.
Kupari, M., Virolainen, J., Koskinen, P., & Tikkanen, M. J. (1993). Short-term heart
rate variability and factors modifying the risk of coronary artery disease in a
population sample. Am J Cardiol, 72(12), 897-903.
La Rovere, M. T., Bigger, J. T., Jr., Marcus, F. I., Mortara, A., & Schwartz, P. J.
(1998). Baroreflex sensitivity and heart-rate variability in prediction of total
cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and
Reflexes After Myocardial Infarction) Investigators. Lancet, 351(9101), 478484.
La Rovere, M. T., Pinna, G. D., Maestri, R., Mortara, A., Capomolla, S., Febo, O., et
al. (2003). Short-term heart rate variability strongly predicts sudden cardiac
death in chronic heart failure patients. Circulation, 107(4), 565-570.
Lavender, A. P., & Nosaka, K. (2008). A light load eccentric exercise confers
protection against a subsequent bout of more demanding eccentric exercise. J
Sci Med Sport, 11(3), 291-298.
Levine, F. M., & De Simone, L. L. (1991). The effects of experimenter gender on
pain report in male and female subjects. Pain, 44, 69-72.

49

Liao, D., Cai, J., Rosamond, W. D., Barnes, R. W., Hutchinson, R. G., Whitsel, E. A.,
et al. (1997). Cardiac autonomic function and incident coronary heart disease:
a population-based case-cohort study. The ARIC Study. Atherosclerosis Risk
in Communities Study. Am J Epidemiol, 145(8), 696-706.
Licciardone, J. C., Fulda, K. G., Stoll, S. T., Gamber, R. G., & Cage, A. C. (2007). A
case-control study of osteopathic palpatory findings in type 2 diabetes
mellitus. Osteopath Med Prim Care, 1, 6.
Lieber, R. L., & Friden, J. (2002). Morphologic and mechanical basis of delayedonset muscle soreness. J Am Acad Orthop Surg, 10(1), 67-73.
Lipsitz, L. A., & Goldberger, A. L. (1992). Loss of 'complexity' and aging. Potential
applications of fractals and chaos theory to senescence. J Am Med Assoc,
267(13), 1806-1809.
Loeser, J. D., & Melzack, R. (1999). Pain: an overview. Lancet, 353(9164), 16071609.
Lorenz, E. N. (1963). Deterministic nonperiodic flow. J Atmospheric Sci, 20(130-41.).
Mair, J., Mayr, M., Muller, E., Koller, A., Haid, C., Artner-Dworzak, E., et al. (1995).
Rapid adaptation to eccentric exercise-induced muscle damage. Int J Sports
Med, 16(6), 352-356.
Malenbaum, S., Keefe, F. J., Williams, A. C., Ulrich, R., & Somers, T. J. (2008). Pain
in its environmental context: implications for designing environments to
enhance pain control. Pain, 134(3), 241-244.
Malik, M., & Camm, A. J. (1993). Components of heart rate variability--what they
really mean and what we really measure. Am J Cardiol, 72(11), 821-822.
Malm, C., Nyberg, P., Engstrom, M., Sjodin, B., Lenkei, R., Ekblom, B., et al. (2000).
Immunological changes in human skeletal muscle and blood after eccentric
exercise and multiple biopsies. J Physiol, 529, 243-262.
Malpas, S. C. (2002). Neural influences on cardiovascular variability: possibilities and
pitfalls. Am J Physiol Heart Circ Physiol, 282(1), H6-20.
Marieb, E. N. (2001). Human anatomy & physiology (5th ed.). Boston: Benjamin
Cummings.
Mathias, C. J., & Bannister, R. (Eds.). (1999). Autonomic failure: a textbook of
clinical disorders of the autonomic nervous system. New York: Oxford
University Press.
McCance, A. J., Thompson, P. A., & Forfar, J. C. (1993). Increased cardiac
sympathetic nervous activity in patients with unstable coronary heart disease.
Eur Heart J, 14(6), 751-757.
McGuiness, J., Vicenzino, B., & Wright, A. (1997). Influence of a cervical
mobilization technique on respiratory and cardiovascular function. Man Ther,
2(4), 216-220.
McHugh, M. P. (2003). Recent advances in the understanding of the repeated bout
effect: the protective effect against muscle damage from a single bout of
eccentric exercise. Scand J Med Sci Sports, 13(2), 88-97.
Melzack, R., & Wall, P. D. (1965). Pain mechanisms: a new theory. Science,
150(699), 971-979.
Mense, S., & Meyer, H. (1988). Bradykinin-induced modulation of the response
behaviour of different types of feline group III and IV muscle receptors. J
Physiol, 398, 49-63.
Merskey, H., & Bogduk, N. (1994). Classification of chronic pain: descriptions of
chronic pain syndromes and definitions of pain terms (2nd ed.). Seattle: IASP
Press

50

Miron, D., Duncan, G. H., & Bushnell, M. C. (1989). Effects of attention on the
intensity and unpleasantness of thermal pain. Pain, 39(3), 345-352.
Mitchell Jr., F. L. (1979). Towards a definition of "somatic dysfunction". Osteopath
Manual Medicine.
Molgaard, H., Sorensen, K. E., & Bjerregaard, P. (1991). Circadian variation and
influence of risk factors on heart rate variability in healthy subjects. Am J
Cardiol, 68(8), 777-784.
Montano, N., Gnecchi-Ruscone, T., Porta, A., Lombardi, F., Malliani, A., & Barman,
S. M. (1996). Presence of vasomotor and respiratory rhythms in the discharge
of single medullary neurons involved in the regulation of cardiovascular
system. J Auton Nerv Syst, 57(1-2), 116-122.
Montano, N., Ruscone, T. G., Porta, A., Lombardi, F., Pagani, M., & Malliani, A.
(1994). Power spectrum analysis of heart rate variability to assess the changes
in sympathovagal balance during graded orthostatic tilt. Circulation, 90(4),
1826-1831.
Mookherjee, S. (2003). Autonomic nervous system and the heart. In M. Aminoff & R.
Daroff (Eds.), Encyclopedia of the neurological sciences (Vol. 1, pp. 531532.). Philadelphia: Elsevier.
Moseley, G. L. (2003). Joining forces - combining cognition-targeted motor control
training with group or individual pain physiology education: a successful
treatment for chronic low back pain. J Man Manip Therap, 11, 88-94.
Moseley, G. L., Brhyn, L., Ilowiecki, M., Solstad, K., & Hodges, P. W. (2003). The
threat of predictable and unpredictable pain: differential effects on central
nervous system processing? Aust J Physiother, 49(4), 263-267.
Moulson, A., & Watson, T. (2006). A preliminary investigation into the relationship
between cervical snags and sympathetic nervous system activity in the upper
limbs of an asymptomatic population. Man Ther, 11(3), 214-224.
Munafo, M. R., & Stevenson, J. (2003). Selective processing of threat-related cues in
day surgery patients and prediction of post-operative pain. Br J Health
Psychol, 8(Pt 4), 439-449.
Nelson, K. E. (2007a). Diagnosing somatic dysfunction. In K. E. Nelson & T. Glonek
(Eds.), Somatic dysfunction in osteopathic family medicine. Philadelphia:
Lippincott Williams & Wilkins.
Nelson, K. E. (2007b). Osteopathic distinctiveness. In K. E. Nelson & T. Glonek
(Eds.), Somatic dysfunction in osteopathic family medicine. Philadelphia:
Lippincott Williams & Wilkins.
Newham, D. J. (1988). The consequences of eccentric contractions and their
relationship to delayed onset muscle pain. Eur J Appl Physiol Occup Physiol,
57(3), 353-359.
Nicholas, A. S., DeBias, D. A., Ehrenfeuchter, W., England, K. M., England, R. W.,
Greene, C. H., et al. (1985). A somatic component to myocardial infarction.
Br. Med. J., 291, 13-17.
Niskanen, J. P., Tarvainen, M. P., Ranta-Aho, P. O., & Karjalainen, P. A. (2004).
Software for advanced HRV analysis. Comput Methods Programs Biomed,
76(1), 73-81.
Nosaka, K., & Clarkson, P. M. (1995). Muscle damage following repeated bouts of
high force eccentric exercise. Med Sci Sports Exerc, 27(9), 1263-1269.
Nosaka, K., Clarkson, P. M., McGuiggin, M. E., & Byrne, J. M. (1991). Time course
of muscle adaptation after high force eccentric exercise. Eur J Appl Physiol
Occup Physiol, 63(1), 70-76.

51

Nosaka, K., Newton, M., & Sacco, P. (2002). Delayed-onset muscle soreness does not
reflect the magnitude of eccentric exercise-induced muscle damage. Scand J
Med Sci Sports, 12(6), 337-346.
Olsen, L. F., & Degn, H. (1985). Chaos in biological systems. Q Rev Biophys, 18(2),
165-225.
Paddon-Jones, D., Muthalib, M., & Jenkins, D. (2000). The effects of a repeated bout
of eccentric exercise on indices of muscle damage and delayed onset muscle
soreness. J Sci Med Sport, 3(1), 35-43.
Pagani, M., Mazzuero, G., Ferrari, A., Liberati, D., Cerutti, S., Vaitl, D., et al. (1991).
Sympathovagal interaction during mental stress. A study using spectral
analysis of heart rate variability in healthy control subjects and patients with a
prior myocardial infarction. Circulation, 83(4 Suppl), II43-51.
Parati, G., Mancia, G., Di Rienzo, M., & Castiglioni, P. (2006). Point: cardiovascular
variability is/is not an index of autonomic control of circulation. J Appl
Physiol, 101(2), 676-678; discussion 681-672.
Parsons, J., & Marcer, N. (2006). Osteopathy: models for diagnosis, treatment and
practice. London: Churchill Livingstone.
Peng, C. K., Mietus, J., Hausdorff, J. M., Havlin, S., Stanley, H. E., & Goldberger, A.
L. (1993). Long-range anticorrelations and non-Gaussian behavior of the
heartbeat. Phys Rev Lett, 70(9), 1343-1346.
Petersen, N., Vicenzino, B., & Wright, A. (1993). The effects of a cervical
mobilisation technique on sympathetic outflow to the upper limb in normal
subjects. Physiother Theory Pract, 9, 145-156.
Pickar, J. G. (2002). Neurophysiological effects of spinal manipulation. Spine J, 2(5),
357-371.
Pikkujamsa, S. (1999). Heart rate variability and baroreflex sensitivity in subjects
without heart disease. University of Oulu, Oulu.
Pober, D. M., Braun, B., & Freedson, P. S. (2004). Effects of a single bout of exercise
on resting heart rate variability. Med Sci Sports Exerc, 36(7), 1140-1148.
Ponikowski, P., Anker, S. D., Chua, T. P., Szelemej, R., Piepoli, M., Adamopoulos,
S., et al. (1997). Depressed heart rate variability as an independent predictor of
death in chronic congestive heart failure secondary to ischemic or idiopathic
dilated cardiomyopathy. Am J Cardiol, 79(12), 1645-1650.
Pool, R. (1989a). Is it chaos, or is it just noise? Science, 243(4887), 25-28.
Pool, R. (1989b). Is something strange about the weather? Science, 243(4896), 12901293.
Proske, U., & Morgan, D. L. (2001). Muscle damage from eccentric exercise:
mechanism, mechanical signs, adaptation and clinical applications. J Physiol,
537(Pt 2), 333-345.
Radespiel-Troger, M., Rauh, R., Mahlke, C., Gottschalk, T., & Muck-Weymann, M.
(2003). Agreement of two different methods for measurement of heart rate
variability. Clin Auton Res, 13(2), 99-102.
Ray, C. A., & Monahan, K. D. (2002). Sympathetic vascular transduction is
augmented in young normotensive blacks. J Appl Physiol, 92(2), 651-656.
Rhudy, J. L., & Meagher, M. W. (2000). Fear and anxiety: divergent effects on human
pain thresholds. Pain, 84(1), 65-75.
Rhudy, J. L., & Meagher, M. W. (2003). Negative affect: effects on an evaluative
measure of human pain. Pain, 104(3), 617-626.
Sandercock, G. R., Bromley, P. D., & Brodie, D. A. (2005). The reliability of shortterm measurements of heart rate variability. Int J Cardiol, 103(3), 238-247.

52

Sato, A., Sato, Y., & Schmidt, R. F. (1979). The effects of somatic afferent activity on
the heart rate. In C. M. Brooks, K. Koizumi & A. Sato (Eds.), Integrative
functions of the autonomic nervous system (pp. 275-282.). Tokyo: University
of Tokyo Press.
Sato, A., Sato, Y., & Schmidt, R. F. (1997). The impact of somatosensory input on
autonomic function. Heidelberg: Springer-Verlag.
Sato, A., & Schmidt, R. F. (1971). Ganglionic transmission of somatically induced
sympathetic reflexes. Pflugers Arch, 326(3), 240-253.
Sato, A., & Schmidt, R. F. (1987). The modulation of visceral functions by somatic
afferent activity. Jpn J Physiol, 37(1), 1-17.
Sato, A., & Swenson, R. S. (1984). Sympathetic nervous system response to
mechanical stress of the spinal column in rats. J Manipulative Physiol Ther,
7(3), 141-147.)
Scheer, F. A., Van Doornen, L. J., & Buijs, R. M. (2004). Light and diurnal cycle
affect autonomic cardiac balance in human; possible role for the biological
clock. Auton Neurosci, 110(1), 44-48.
Schott, G. D. (1994). Visceral afferents: their contribution to 'sympathetic dependent'
pain. Brain, 117(2), 397.
Schott, G. D. (1999). Pain and the sympathetic nervous system. In C. J. Mathias & R.
Bannister (Eds.), Autonomic failure: a textbook of clinical disorders of the
autonomic nervous system (pp. 520-526.). Oxford: Oxford University Press.
Siddall, P. J., & Cousins, M. J. (1997). Spinal pain mechanisms. Spine, 22(1), 98-104.
Simon, R., Vicenzino, B., & Wright, A. (1997). The influence of an anteroposterior
accessory glide of the glenohumeral joint on measures of peripheral
sympathetic nervous system function in the upper limb. Man Ther, 2(1), 1823.
Sleight, P., La Rovere, M. T., Mortara, A., Pinna, G., Maestri, R., Leuzzi, S., et al.
(1995). Physiology and pathophysiology of heart rate and blood pressure
variability in humans: is power spectral analysis largely an index of baroreflex
gain? Clin Sci (Lond), 88(1), 103-109.
Smith, W. B., Gracely, R. H., & Safer, M. A. (1998). The meaning of pain: cancer
patients' rating and recall of pain intensity and affect. Pain, 78, 123-129.
Snell, R. S. (2001). Clinical neuroanatomy for medical students (5th ed.).
Philadelphia: Lippincott, Williams & Wilkins.
The new Collins dictionary and thesaurus. (1988).Glasgow: Collins.
Stauss, H. M. (2003). Heart rate variability. Am J Physiol Regul Integr Comp Physiol,
285(5), R927-931.
Stein, P. K., & Kleiger, R. E. (1999). Insights from the study of heart rate variability.
Annu Rev Med, 50, 249-261.
Sterling, M., Jull, G., & Wright, A. (2001). Cervical mobilisation: concurrent effects
on pain, sympathetic nervous system activity and motor activity. Man Ther,
6(2), 72-81.
Stone, C. (1999). Science in the art of osteopathy: osteopathic principles and
practice. Cheltenham: Stanley Thornes Ltd.
Sztajzel, J. (2004). Heart rate variability: a noninvasive electrocardiographic method
to measure the autonomic nervous system. Swiss Med Wkly, 134(35-36), 514522.
Tack, C. J., Lenders, J. W., Willemsen, J. J., van Druten, J. A., Thien, T., Lutterman,
J. A., et al. (1998). Insulin stimulates epinephrine release under euglycemic
conditions in humans. Metabolism, 47(3), 243-249.

53

Tarkiainen, T. H., Timonen, K. L., Tiittanen, P., Hartikainen, J. E., Pekkanen, J.,
Hoek, G., et al. (2005). Stability over time of short-term heart rate variability.
Clin Auton Res, 15(6), 394-399.
Task Force. (1996). Heart rate variability: standards of measurement, physiological
interpretation and clinical use. Task Force of the European Society of
Cardiology and the North American Society of Pacing and Electrophysiology.
Circulation, 93(5), 1043-1065.
Taylor, J. A., Carr, D. L., Myers, C. W., & Eckberg, D. L. (1998). Mechanisms
underlying very-low-frequency RR-interval oscillations in humans.
Circulation, 98(6), 547-555.
Terkelsen, A. J., Andersen, O. K., Molgaard, H., Hansen, J., & Jensen, T. S. (2004).
Mental stress inhibits pain perception and heart rate variability but not a
nociceptive withdrawal reflex. Acta Physiol Scand, 180(4), 405-414.
Terui, N., & Koizumi, K. (1984). Responses of cardiac vagus and sympathetic nerves
to excitation of somatic and visceral nerves. J Auton Nerv Syst, 10(2), 73-91.
Thayer, J. F., & Friedman, B. H. (2002). Stop that! Inhibition, sensitization, and their
neurovisceral concomitants. Scand J Psychol, 43(2), 123-130.
Thayer, J. F., Hall, M., Sollers, J. J., 3rd, & Fischer, J. E. (2006). Alcohol use, urinary
cortisol, and heart rate variability in apparently healthy men: evidence for
impaired inhibitory control of the HPA axis in heavy drinkers. Int J
Psychophysiol, 59(3), 244-250.
Tsuji, H., Larson, M. G., Venditti, F. J., Jr., Manders, E. S., Evans, J. C., Feldman, C.
L., et al. (1996). Impact of reduced heart rate variability on risk for cardiac
events. The Framingham Heart Study. Circulation, 94(11), 2850-2855.
Tuchin, P. J. (1998). The effect of chiropractic spinal manipulative therapy on
salivary cortisol levels. Australasian Chiro and Osteo, 7(2), 86-92.
Udupa, K., Sathyaprabha, T. N., Thirthalli, J., Kishore, K. R., Lavekar, G. S., Raju, T.
R., et al. (2007). Alteration of cardiac autonomic functions in patients with
major depression: a study using heart rate variability measures. J Affect
Disord, 100(1-3), 137-141.
Uusitalo, A. L., Laitinen, T., Vaisanen, S. B., Lansimies, E., & Rauramaa, R. (2004).
Physical training and heart rate and blood pressure variability: a 5-yr
randomized trial. Am J Physiol Heart Circ Physiol, 286(5), H1821-1826.
Vicenzino, B., Cartwright, T., Collins, D., & Wright, A. (1998). Cardiovascular and
respiratory changes produced by lateral glide mobilization of the cervical
spine. Man Ther, 3(2), 67-71.
Vicenzino, B., Collins, D., Benson, H., & Wright, A. (1998). An investigation of the
interrelationship between manipulative therapy-induced hypoalgesia and
sympathoexcitation. J Manipulative Physiol Ther, 21(7), 448-453.
Vigo, D. E., Guinjoan, S. M., Scaramal, M., Siri, L. N., & Cardinali, D. P. (2005).
Wavelet transform shows age-related changes of heart rate variability within
independent frequency components. Auton Neurosci, 123(1-2), 94-100.
Vincent, H. K., & Vincent, K. R. (1997). The effect of training status on the serum
creatine kinase response, soreness and muscle function following resistance
exercise. Int J Sports Med, 18, 431-437.
Viola, A. U., Simon, C., Ehrhart, J., Geny, B., Piquard, F., Muzet, A., et al. (2002).
Sleep processes exert a predominant influence on the 24-h profile of heart rate
variability. J Biol Rhythms, 17(6), 539-547.
Vlaeyen, J. W., & Crombez, G. (1999). Fear of movement/(re)injury, avoidance and
pain disability in chronic low back pain patients. Man Ther, 4(4), 187-195.

54

Vlaeyen, J. W., & Linton, S. J. (2000). Fear-avoidance and its consequences in

chronic musculoskeletal pain: a state of the art. Pain, 85(3), 317-332.
Vollenweider, P., Tappy, L., Randin, D., Schneiter, P., Jequier, E., Nicod, P., et al.
(1993). Differential effects of hyperinsulinemia and carbohydrate metabolism
on sympathetic nerve activity and muscle blood flow in humans. J Clin Invest,
92(1), 147-154.
Ward, R. C. (Ed.). (2003). Foundations for osteopathic medicine. Philadelphia:
Lippincott Williams & Wilkins.
Weerakkody, N. S., Whitehead, N. P., Canny, B. J., Gregory, J. E., & Proske, U.
(2001). Large-fiber mechanoreceptors contribute to muscle soreness after
eccentric exercise. J Pain, 2(4), 209-219.
Willard, F. H. (2007). Nocioception and spinal facilitation: spinal level, The
pathophysiology of pain. Auckland.
Wright, A. (1995). Hypoalgesia post-manipulative therapy: a review of a potential
neurophysiological mechanism. Man Ther, 1(1), 11-16.
Yamanaka, Y., & Honma, K. (2006). Cardiovascular autonomic nervous response to
postural change in 610 healthy Japanese subjects in relation to age. Auton
Neurosci, 124(1-2), 125-131.
Yasuma, F., & Hayano, J. (2004). Respiratory sinus arrhythmia: why does the
heartbeat synchronize with respiratory rhythm? Chest, 125(2), 683-690.
Yu, J. G., Carlsson, L., & Thornell, L. E. (2004). Evidence for myofibril remodeling
as opposed to myofibril damage in human muscles with DOMS: an
ultrastructural and immunoelectron microscopic study. Histochem Cell Biol,
121(3), 219-227.
Zhang, J., Dean, D., Nosco, D., Strathopulos, D., & Floros, M. (2006). Effect of
chiropractic care on heart rate variability and pain in a multisite clinical study.
J Manipulative Physiol Ther, 29(4), 267-274.
Zhong, Y., Jan, K. M., Ju, K. H., & Chon, K. H. (2006). Quantifying cardiac
sympathetic and parasympathetic nervous activities using principal dynamic
modes analysis of heart rate variability. Am J Physiol Heart Circ Physiol,
291(3), H1475-1483.
Zobel, A., Wellmer, J., Schulze-Rauschenbach, S., Pfeiffer, U., Schnell, S., Elger, C.,
et al. (2004). Impairment of inhibitory control of the hypothalamic pituitary
adrenocortical system in epilepsy. Eur Arch Psychiatry Clin Neurosci, 254(5),
303-311.

55

Section 2: Manuscript
Note
This manuscript has been prepared in accordance with the Guide for Authors for the International
Journal of Osteopathic Medicine (See Appendix E).

56

The effect of pain associated with delayed

onset muscle soreness on the autonomic
nervous system as measured by heart rate
variability

57

The effect of pain associated with delayed

onset muscle soreness on the autonomic
nervous system as measured by heart rate
variability

Larissa Morgan
School of Health Science
Unitec New Zealand
Private Bag 92025, Auckland
New Zealand

Tel: +64 9 815 4321 x8642

Fax: +64 9 815 4573
Email: larissam@woosh.co.nz

58

Abstract
Background: A central concept within osteopathy is that disturbance of
musculoskeletal or visceral structures can perturb the autonomic nervous system
(ANS). Such perturbation is postulated to generate reflexes that can affect other
structures with the same autonomic innervation. Within osteopathy, the effects of this
purported process are considered amenable to manual therapy techniques, such as
spinal manipulation. However, scientific research investigating this process is limited
and often inconclusive, and despite evidence demonstrating that spinal manipulation
affects the ANS, the clinical relevance of such an effect has had limited discussion.
Objective: The objective of this study was to examine the effect of a mild to
moderate musculoskeletal disturbance, such as delayed onset muscle soreness
(DOMS), on the ANS as measured by heart rate variability (HRV), in healthy young
males.
Methods: A time series single-subject design was conducted on six subjects (age
range 23 to 36 years). Heart rate was recorded daily for 15 minutes over five
consecutive days to establish baseline (Phase A) and then daily for nine consecutive
days after an exercise protocol to induce DOMS (Phase B). Pain intensity scores
were recorded twice daily throughout Phase B. Frequency spectra for HRV data was
extracted and five minutes of normalised R-R intervals were plotted with pain
intensity data against time. Visual analysis of changes to level, trend, and stability of
HRV and pain intensity data was then performed.
Results: Within the confines of this study, the results indicated that changes to HRV
did not occur as a result of pain associated with DOMS. Although slight differences
in the stability of HRV data and slope of trend line occurred in some subjects, no
consistent pattern emerged that was attributable to DOMS.
Conclusion: Delayed onset muscle soreness was not clearly associated with changes
to the autonomic output to the heart, as measured by HRV, in healthy males.

Key terms: Autonomic nervous system; Heart rate variability; Delayed onset muscle
soreness; time-series design.

59

Introduction
A central concept within osteopathic texts is that disturbance of musculoskeletal
structures can perturb the autonomic nervous system (ANS). Perturbation of the ANS
is believed to potentially influence the function of viscera or other musculoskeletal
structures supplied by common autonomic segments.1, 2 The osteopathic concept that
disturbance to visceral and musculoskeletal structures can have effects elsewhere in
the body via the ANS, is commonly described in historical and anecdotal reports but
has not been adequately investigated. This concept also provides part of the rationale
for the osteopathic treatment approach and the use of spinal manipulation techniques.
Although research indicates that noxious and long-term musculoskeletal stimuli can
produce changes in the ANS,3-5 the effects from mild to moderate musculoskeletal
disturbance are less apparent.6-10

Osteopathic literature has begun to gather evidence on one aspect of the concept that
musculoskeletal or visceral disturbance can perturb the ANS: namely, whether
manual therapy techniques, such as spinal manipulation, influence autonomic activity.
Recent evidence has demonstrated that spinal manipulation appears to exert an effect
on the ANS,9, 11, 12 however, these studies do not indicate the magnitude of effect nor
whether the effect on the ANS is favourable or unfavourable. Furthermore, it is not
clear how clinically beneficial techniques that putatively influence the ANS are, nor
how necessary such techniques are to patient care.

Recently, a case series study by Grimm et al. investigated soft tissue injury and ANS
indices.7 Although Grimm reported alterations in cardiac and peripheral autonomic
activity amongst injured subjects, there is scant literature investigating a possible
relationship between soft tissue injury and ANS perturbation. With few studies, and
no clear physiological mechanisms, evidence to support or refute the osteopathic
concept that musculoskeletal disturbance can perturb the ANS is lacking.
Furthermore, it is unclear whether it necessarily follows that such ANS perturbation
will have an unfavourable effect. If osteopathic techniques can modulate ANS
activity, do they evoke an ANS response beyond any localised or short-term general
effect, to ameliorate the so-claimed effects further afield? Establishing the nature and

60

significance of any purported links is important to not only evaluate tenets within
osteopathy, but may be of clinical relevance to those with acute injury or those in
chronic pain states.

Delayed onset muscle soreness (DOMS) is temporary soreness commonly

experienced after unaccustomed or strenuous exercise. 16-18 An initial step in
establishing the nature and significance of the purported links between the ANS and
musculoskeletal structures, is to undertake preliminary work to establish 1) if DOMS
is a viable model for investigating this ANS-injury relationship, and 2) if there is an
association between DOMS and ANS disturbance that is consistent with the
osteopathic concept. The aim of this preliminary study was to determine whether the
physiological effects of DOMS, as a model of mild to moderate musculoskeletal pain,
would influence the ANS as measured by heart rate variability (HRV).

61

Methods
Design
A time-series A-B experimental design was used for this preliminary study. Timeseries or single-subject designs are a useful low-cost approach to provide preliminary
information about possible causal relationships.13-15 Such designs are logistically
simple and may provide avenues for further investigation with more robust group
designs such as randomised, controlled, experimental studies.

Subjects
Subjects were recruited via word of mouth and poster advertising at Unitec New
Zealand. All subjects satisfied exclusion and inclusion criteria. Exclusion criteria
were: disorders of the immune, endocrine, and musculoskeletal systems; recent or
unresolved trauma; psychological disorders; and medication known to influence the
ANS or cardiovascular system. Exclusion criteria also included participation in highintensity or frequent cardiovascular or resistance exercise (five or more days per
week), such as high-intensity cycling, running, or weight training. Subjects were
required to be non-smokers, with a body mass index (BMI) between 18.5 and 30, and
not experiencing pain or discomfort at the time of recruitment. The Unitec Research
Ethics Committee approved the study and written informed consent was obtained
from all subjects [see Appendix A].

62

Variables and Operational Definitions

Independent variable
The intended tissues in which DOMS was to be induced were the elbow flexor, and
possibly forearm flexor, muscles of the non-dominant arm. The manner in which
DOMS was induced was consistent with previous studies on DOMS,16-18 utilising
eccentric contraction of the elbow and forearm flexor muscles to produce controlled
elbow extension to the end of range. The maximum weight able to be performed for a
single repetition of elbow flexion, or one repetition maximum (1RM), was
ascertained, and isokinetic eccentric contraction of the elbow and forearm flexors was
performed using a dumbbell weight calculated to be 40-50% of the 1RM. Completion
of the exercise protocol was determined to be failure to complete an eccentric
contraction, that is, inability to control the decent of the dumbbell.

Dependant variable
A wireless heart rate monitor (Polar S810i, Polar Electro Oy, Finland) was used to
collect consecutive beat-to-beat electrocardiogram signal, which was later analysed in
HRV Analysis Software v1.1 (The Biomedical Signal Analysis Group, Kuopio,
Finland). The Polar S810i has been validated and good agreement with other
electrocardiogram instruments has been demonstrated.19, 20 All data was stored on a
personal computer for off-line data analysis.

The Short Form McGill Pain Questionnaire (SF-MPQ) was used to measure sensory
and affective qualities of pain and perceived pain intensity.21 A standardised 100mm
horizontal visual analogue scale (VAS) contained in the SF-MPQ, anchored on the
left with no pain and the right with worst possible pain, was also used to measure
pain intensity. The SF-MPQ21, 22 and VAS23, 24 are widely used in research and are
generally considered to be valid and reliable instruments for pain assessment.

63

Procedure
The study was divided into two phases as illustrated in Figure 1. Phase A consisted of
heart rate recording for 15 minutes per day, between the hours of 1600 and 2000, over
five consecutive days. Phase B involved an eccentric exercise protocol on day six
that was intended to induce DOMS, and continued daily heart rate recording and
completion of the SF-MPQ approximately every 12 hours until the end of data
collection on day 14.

HRV

HRV and SF-MPQ

Phase A

10 11 12 13 14

Phase B

TIME

Exercise

Figure 1
Overview of study design.
Phase A comprised of heart rate recording for 15 minutes per day, between the hours of 1600
and 2000, over five consecutive days. Phase B comprised an exercise protocol the morning of
day six, continued daily heart rate recording, and pain intensity reporting every 12 hours.

Each subject received a project information sheet [see Appendix B], operational
instructions for the heart rate monitor [see Appendix C], and a DOMS information
sheet [see Appendix D]. Phase B of the data collection period was outlined to
subjects including the exercise protocol. Correct use of the heart rate monitor was
demonstrated, and subjects practiced placement of equipment and recording of heart
rate in a seated position until deemed by the investigator to be competent and
confident with operation. Each subject was instructed on the daily protocol of data
collection, and requested to refrain from exercise and from consumption of
stimulants, alcohol, and food three hours prior to recording sessions. Subjects were
supplied a nature documentary DVD (The Living Planet)25 to watch during heart rate
recording. Use of the documentary was intended to provide similar recording
conditions between measurement sessions as data collection was undertaken in the
subjects home. The documentary was pre-screened by the investigator and did not

64

contain any content that would potentially startle subjects or evoke strong emotional
responses.

Intervention
Subjects performed the exercise protocol during the morning of day six. Pain
intensity scores were recorded prior to the exercise. The 1RM for the non-dominant
arm was determined, and a dumbbell of approximately 40-50% of the 1RM selected.
Subjects were seated at one end of a standard gym training bench and instructed on
positioning to provide full elbow extension and adequate clearance for the descent of
the dumbbell. Eccentric contraction of the elbow and forearm flexors of the nondominant arm was performed to a count of four seconds. A one second recovery was
included where subjects were assisted in return of the dumbbell to the start position
(fully flexed elbow). Subjects rested for 30 seconds between each set of ten
repetitions and the protocol repeated until subjects failed to complete an eccentric
contraction (i.e. controlled descent of the dumbbell). A summary of the exercise
protocol for each subject is presented in Table 1.

Table 1

Exercise summary for all subjects

1RM (kg)

Weight used (kg)

Sets performed

S1

20

10

S2

20

10

8.4

S3

20

10

S4

22

12.5

8.4

S5

17

S6

17

Mean

19.3

9.5

6.5

SD

1.9

2.6

1.8

All subjects recorded pain intensity scores immediately after the exercise protocol.
Subjects continued to record heart rate from home in the same manner as Phase A,
with the addition of the SF-MPQ each morning and evening until the end of Phase B.

65

Data Analysis
Data extraction
Beat to beat (R-R) intervals were extracted from the heart rate monitor using
proprietary software (Polar Precision Performance SW, Polar Electro Oy, Finland).
Raw R-R interval data was exported into Microsoft Excel for visual inspection.
Artifact and ectopic beats were replaced with a beat interpolated between the previous
and subsequent normal beats using a method described by the Task Force of the
European Society of Cardiology and the North American Society of Pacing and
Electrophysiology.26 Consistent with established guidelines, data was excluded from
analysis if ectopy was greater than 5% of the recording.26 A clear five-minute period
of heart rate data was extracted from the last two thirds of the 15-minute recording to
minimise movement ectopy. Normalised data was imported into HRV Analysis
Software v1.1 (The Biomedical Signal Analysis Group, Kuopio, Finland). The
software transformed normalised data into statistical time domain measures, a
Poincar plot, and frequency spectra quantified by autoregressive and Fast Fourier
Transform (FFT) (Figure 2). These measures are widely used in research employing
HRV and provide a number of methods to interpret variations in heart rate.26-29

66

S6 D2.txt
Page 1/1

Heart Rate Variability Analysis

RR Interval Time Series

972

RRI (s)

0
1
0.8
0

100

200

300

400

500
Time (s)

600

700

800

900

300

400

500
Time (s)

600

700

800

900

Selected RR Interval Tim e Series

RRI (s)

0.1
0
-0.1
0

100

200

Poincare Plot* SD1 = 18.6 m s (Short-term HRV)

Tim e Domain Results

Variable
Statistical M easures
Mean RR*
STD
Mean HR*
STD
RMSSD
NN50
pNN50
Geometric M easures
RR triangular index
TINN

Units

Value

(s )
(s )
(1/m in)
(1/m in)
(m s )
(count)
(%)

0.984
0.037
61.07
2.45
26.1
51
5.2

(m s )

0.080
205.0

SD2 = 55.5 m s

(Long-term HRV)

1.15
1.1

SD2

SD1

1.05

RRI

n+1

(s)

1
0.95
0.9
0.85

Distributions*

0.8
0.75
0.8

0.9
1
RRI (s)

1.1

55

0.8

60 65 70 75
HR (beats/min)

0.9

1.1

RRIn (s)

Frequency Domain Results

-3
x 10

Non Param etric Spectrum (FFT)

Parametric Spectrum (AR Model)

0.01

PSD (s2/Hz)

PSD (s2/Hz)

0.005

0.1

Frequency
Peak
Band
(Hz)
VLF
0.0391
LF
0.0488
HF
0.2402
LF/HF

0.2
0.3
Frequency (Hz)

Power
(m s 2)
64
394
123

Power
(%)
11.0
67.8
21.2
3.205

0.4

76.2
23.8

4
2
0

0.5

Power
(n.u.)

0.1

Frequency Peak
Band
(Hz)
VLF
0.0000
LF
0.0703
HF
0.2363
LF/HF

11-Sep-2007 - H RV Analy sis Sof tware v 1.1

*Res ults are calculated from the non-detrended s elected RRI s ignal.

0.2
0.3
Frequency (Hz)

Power
(m s 2)
0
592
115

0.4

Power
(%)
0.0
83.7
16.3
5.141

0.5

Power
(n.u.)
90.4
17.6

The Biom edical Signal Analy sis Group

D epartm ent of Applied Phy sics
U niv ersity of Kuopio, F inland

Figure 2
Typical Heart Rate Variability Analysis report
Example HRV Analysis report (subject six, day two) illustrating tachogram of normalised R-R interval
data, and transformation of data into statistical time domain measures, a Poincar plot, and parametric
(autoregressive) and non-parametric (Fast Fourier Transform) frequency spectra.

67

For each subject, normalised units (n.u.) of the high frequency (HF) and low
frequency (LF) parameters of HRV were taken from FFT, and plotted with pain
intensity data (VAS units: mm) against time. For the purpose of visual analysis, the
mean of the five baseline data points was calculated for each HRV parameter. The
two standard deviation limits were computed from the mean of the baseline data (days
1-5) and added to each plot of HRV versus time. Trend lines, calculated using simple
linear regression in Microsoft Excel, were also added to Phase A and Phase B of each
graph. Consistent with literature on single-subject designs, visual analysis of changes
in level (i.e. above or below the level of the baseline), trend (upward-sloping,
downward sloping, stationary), and stability of HRV data between phases was
performed.13-15

68

Results
Six healthy males aged 23 to 36 were recruited into the study. Subject characteristics
are presented in Table 2.

Table 2

Subject characteristics

ID
No.

Age

Occupation

36

Height (m)

Weight (kg)

BMI (kg/m )

Routine
physical
activity

Full time student

1.78

70

22.1

Gym, running

30

Full time student

1.75

79

25.6

Yoga, cycling

33

Part time
lecturer and land
surveyor

1.66

70

25.4

Squash,
hiking

29

Part time
student and
hospitality
worker

1.83

95

28.4

Gym

23

Full time winery

cellar-hand

1.75

75

24.5

Occupation,
tennis

29

Full time student

1.83

74

22.1

Cycling

All subjects completed the 14 day study. Phase A of data collection consisted of daily
heart rate recording for five consecutive days, between the hours of 1600 and 2000, to
establish baseline HRV. Phase B of data collection consisted of the exercise protocol
on day six which was intended to induce DOMS, continued daily heart rate recording,
and pain intensity reporting every 12 hours until the end of day 14. Four subjects (S1,
S3, S4, and S5) had two days of missing heart rate data. This was due either to
excessive artifact, possibly as a result of electromagnetic interference with the heart
rate monitor equipment, or from human error. For the purpose of analysis, pain
intensity data was subdivided into pre-exercise (day six), immediate post-exercise
(day six), pre-DOMS (days 6-7), DOMS period (days 7-9), and recovery period (days
10-14). The Phase B HRV data was subdivided into pre-DOMS (day 6), DOMS
period (days 7-9), and recovery period (days 10-14).
69

Induction of pain associated with DOMS as measured by VAS

Both Figure 3 (High Frequency HRV and VAS versus time) and Figure 4 (Low
Frequency HRV and VAS versus time) show pain intensity data for each subject.
Pain intensity data was subdivided into pre-exercise (day six), immediate postexercise (day six), pre-DOMS (days 6-7), DOMS period (days 7-9), and recovery
period (days 10-14). The exercise protocol intended to induce DOMS was performed
during the morning of day six after collecting pre-exercise pain intensity scores for
each subject. Completion of the exercise protocol was determined to be the inability
to perform one more eccentric contraction (i.e. control the descent of the dumbbell).
For all subjects the pain intensity scores increased immediately after completion of
the exercise. In all subjects except one (S4), pain levels then reduced by the evening
of day six. During this time S4s pain intensity score remained the same, although S4
had reported a lower immediate post-exercise score than other subjects.
During the period in which DOMS was expected to occur (days 7, 8, 9), the pain
intensity scores increased for all subjects except S5. For S5, pain intensity on day
eight (VAS = 5mm) barely rose beyond that seen at the end of day six (VAS = 3mm).
One subject, S6, demonstrated a classic DOMS pattern16, 30 as evidenced by reported
pain intensity. The first increase in pain intensity for S6 was seen immediate postexercise (VAS = 23mm). Pain intensity reduced to zero by the end of day six,
indicating full recovery from the exercise protocol. Pain intensity for S6 increased
again during day eight (VAS = 42mm), the period in which DOMS was expected to
occur. During the recovery period, pain intensity scores for S6 steadily declined to
zero over the remaining six days of data collection, indicating full recovery from
DOMS.

Delayed onset muscle soreness was also apparent in S1, S2, S3, and S4, although
these subjects showed various patterns compared with S6. Subject 4 (S4) reported an
injury to the low back/buttock region and non-dominant arm as a result of a fall
during the evening of day six, and therefore pain intensity scores appear to show no
short-term recovery from the day six exercise protocol. For S2 and S3, the pain
intensity scores show a relatively slow recovery rate from the exercise protocol. In
S2, the immediate post-exercise VAS score reduced by 50% at the end of day six to

70

11mm. This score was followed by peak pain intensity one day later on the morning
of day seven (VAS = 66mm), the peak of DOMS for S2. In S3, the recovery rate
from the exercise protocol was slower, with the immediate post-exercise score
reducing by 23% by the end of day seven to a VAS of 47mm. This score was
followed by peak pain intensity one day later on day eight (VAS = 62mm), the peak
of DOMS for S3.

During the period in which DOMS was expected (days 7, 8, 9), the pain intensity
scores for S5 indicate that the exercise protocol did not induce DOMS in this subject.
The pain intensity scores for S1 during the expected DOMS period only reached 55%
of the immediate post-exercise score of 70mm; however, pain intensity scores indicate
delayed soreness during the expected timeframe of 24-48 hours post-exercise. During
S1s recovery period, pain intensity declined to zero then increased again to 23mm on
day ten. On day ten, S1 reported mild soreness in the hamstring and oblique
abdominal muscles as the result of a routine gym workout on day nine. This increase
in pain intensity was likely due to exercise-induced soreness unrelated to the
experiment. After day ten, pain intensity for S1 gradually declined to zero towards
the end of data collection on day 14 indicating full recovery from muscle soreness
either related or unrelated to the experiment.

In summary, the exercise protocol resulted in reports of pain consistent with DOMS in
S2, S3, S4, and S6, as evidenced by pain intensity scores. The increase in pain
intensity reported by subjects occurred during days 7-9, correlates with literature on
the temporal nature of DOMS (i.e. 24-48 hours after the unaccustomed exercise on
day six).16-18 The exercise protocol resulted in somewhat less satisfactory DOMS in
S1 during days 7-9, and in one subject (S5) DOMS did not occur. As such the high
and low frequency HRV data will only be discussed for S1, S2, S3, S4, and S6.

Normalised high frequency parameter of heart rate variability

The high frequency (HF) parameter is nominally considered to range between 0.150.4 Hz, but also contributes to the low frequency HRV parameter (0.05-0.15 Hz).26
The HF parameter of HRV is clearly established as being dominated by

71

parasympathetic activity from the vagus nerve.26, 31 Parasympathetic activity is

known to lower heart rate and the force of cardiac contraction, and increases the beatto-beat variability of heart rate. A shift towards increased HF in the HRV of a subject
indicates increasing parasympathetic activity.26, 32

Phase A Baseline HF HRV data

Figure 3 (High Frequency HRV and VAS versus time) shows normalised high
frequency HRV data and pain intensity data across Phase A and B for the six subjects
tested. In S1 and S6, HF data showed a relatively stable baseline. For S2, HF data
during Phase A trends upwards. For S3, Phase A HF data shows a relative trend
downwards, but this trend is well contained within two standard deviations of the
baseline mean. For S4, baseline data appears unstable. The HF HRV baseline data
did not exceed two standard deviations of the baseline mean during Phase A for any
of the five subjects.

Phase B pre-DOMS, DOMS and recovery period HF HRV data

In Phase B, HRV data was subdivided into pre-DOMS (day six), DOMS period (days
7-9), and recovery period (days 10-14). In subjects S1 and S6, HF HRV data show no
changes during the DOMS period at days 7-9, although S6 showed less stable HF
readings from day eight onwards. In S2, an upward-sloping baseline was followed by
a level trend line with stable HF data at pre-DOMS into DOMS period. In S3, the
downward-sloping baseline levelled off but with more unstable HF readings in Phase
B. In S4, HF data showed no distinguishable difference during Phase B, with
unstable readings pre- and post-DOMS, and no change in trend.

In those subjects in whom DOMS was achieved (S1, S2, S3, S4, S6), no consistent
pattern in the HF data was found that would suggest a relationship between pain
associated with DOMS and HRV. In the subject demonstrating a classic DOMS pain
pattern (S6), the Phase B HF HRV data showed greater fluctuation compared to
baseline and some higher readings, but these readings were not consistently greater
than the baseline mean. In three of the five subjects in whom DOMS was achieved

72

(S3, S4, and S6), the recovery period HF data appeared less stable day to day. In S2,
the HF HRV data throughout Phase B was slightly below the baseline mean and level
compared to an upward-sloping baseline. Data from S2 also showed increased
fluctuation in Phase B data points compared with baseline, but remained stable
overall. In S3, the HF HRV data in Phase B was slightly below the baseline mean,
showed a slight upward-sloping trend line compared to the downward-sloping
baseline, and had greater fluctuation and instability compared to baseline. In
summary, changes to HF HRV data could not be related to pain intensity in the five
subjects in whom DOMS was satisfactorily achieved.

73

S2 - HF & VAS

VAS

HF (n.u.)

S1 - HF & VAS

HF (n.u.)

VAS

100

100

90

90

80

100

100

90

90

80

80

70

70

60

60

50

50

40

40

30

30

80

70

70

60

60

50

50

40

40

30

30

20

20

20

20

10

10

10

10

10

11

12

13

14

0
0

15

10

11

12

13

14

15

tim e (days)

time (da ys)

S3 - HF & VAS

VAS

HF (n.u.)

S4 - HF & VAS

HF (n.u.)

VAS

110

110

100

100

100

100

90

90

90

90

80

80

80

80

70

70

70

70

60

60

60

60

50

50

50

50

40

40

40

40

30

30

30

30

20

20

20

20

10

10

10

10

0
-10 0

10

11

12

13

14

0
15 -10

0
1

10

11

12

13

14

15

time (days)

S5 - HF & VAS

HF (n.u.)

0
0

time (days)

VAS

S6 - HF & VAS

HF (n.u.)

VAS

100

100

110

110

100

100

90

90

90

90

80

80

80

80

70

70

60

60

50

50

40

40

40

30

30

30

30

20

20

20

20

10

10

10

10

70

70

60

60

50

50
40

-10
0

10

11

12

13

14

15

0
0

10

11

12

time (days)

time (days)

Key:

Phase A
HRV
Baseline
mean

Phase B
HRV

Exercise protocol
day six

2SD

VAS

Figure 3
High Frequency HRV and VAS versus time.
Scatter plot representing five minutes of normalised HF HRV data collected between the hours of 1600
and 2000 over 14 days, with trend lines added to Phase A and Phase B HRV data. Line graph across
days 6-14 representing VAS data collected pre-exercise, immediate post-exercise, end of day six and
every 12 hours from day 7-14. Baseline mean calculated from day 1-5 HF HRV data points. Four
subjects (S1, S2, S4, S5) have one HF HRV data point missing due to human error, and one data point
excluded due to ectopy exceeding 5%.

74

13

14

15

Normalised low frequency parameter of heart rate variability

The low frequency (LF) parameter of HRV is nominally considered to range between
0.05-0.15 Hz. Studies indicate that the LF parameter of HRV is mediated by both
sympathetic and parasympathetic activity to the heart.26, 31, 33 Baroreceptor activity is
thought by some to be the predominant influence on LF,34 although data from
animals35 and humans36 suggests a medullary origin. Since LF is not specific for
either ANS division it is usually not considered a general index of sympathetic
cardiac control or sympatho-vagal balance.26

Phase A Baseline LF HRV data

Figure 4 (Low Frequency HRV and VAS versus time) shows normalised low
frequency HRV data and VAS data across Phase A and B for the six subjects tested.
In S1 and S6, LF data showed a relatively stable baseline. For S2, LF data during
Phase A trends downwards. For S3, Phase A LF data shows a relative trend upwards,
but this trend is well contained within two standard deviations (2SD). For S4,
baseline LF data appears unstable. The LF HRV baseline data did not exceed 2SD
during Phase A for any of the five subjects.

Phase B pre-DOMS, DOMS and recovery period LF HRV data

In Phase B, HRV data was subdivided into pre-DOMS (day six), DOMS period (days
7-9), and recovery period (days 10-14). In S6, LF HRV data showed a drop during
day eight (i.e. within the DOMS period) that exceeded 2SD, followed by less stable
LF readings from day eight onwards. For S2, a downward-sloping baseline was
followed by a level trend line with stable LF data at immediate post-exercise and preDOMS into the DOMS period. In S3, the upward-sloping baseline levelled off during
Phase B, and the data was less stable overall than baseline. In S4, LF data showed no
distinguishable difference during Phase B, with unstable readings pre- and postDOMS, and no change in trend.

In those subjects in whom DOMS was achieved (S1, S2, S3, S4, S6), no consistent
pattern in the LF data was found that would suggest a relationship between pain
75

associated with DOMS and HRV. In the subject demonstrating a classic DOMS pain
pattern (S6), the Phase B LF HRV data showed greater fluctuation compared to
baseline and some lower readings, but these readings were not consistently lower than
the baseline mean. In three of the five subjects in whom DOMS was achieved (S3,
S4, and S6), the recovery period LF data appeared less stable day to day than the preDOMS period. In S2, the LF HRV data throughout Phase B was slightly above the
baseline mean and level compared to a downward-sloping baseline. Data from S2
also showed increased fluctuation in Phase B data points compared with baseline, but
remained stable overall. In S3, the LF HRV data in Phase B was slightly above the
baseline mean, showed a slight down-slope compared to an upward-sloping baseline,
and had greater fluctuation and instability compared to baseline. In summary,
changes to LF HRV data could not be related to pain intensity in the five subjects in
whom DOMS was satisfactorily achieved.

76

S1 - LF & VAS

VAS

LF (n.u.)

S2 - LF & VAS

LF (n.u.)

VAS

100

100

100

90

90

90

90

80

80

80

80

70

70

70

70

60

60

60

60

50

50

50

50

40

40

40

40

30

30

30

30

20

20

20

20

10

10

10

10

10

11

12

13

14

15

100

0
0

time (days)

10

11

12

13

14

15

time (days)

S3 - LF & VAS

VAS

LF (n.u.)

S4 - LF & VAS

LF (n.u.)

VAS

110

110

100

100

100

100

90

90

90

90

80

80

80

80

70

70

70

70

60

60

60

60

50

50

50

50

40

40

40

40

30

30

30

30

20

20

20

20

10

10

10

10

-10 0

10

11

12

13

14

0
0

15 -10

10

11

12

13

14

15

time (days)

time (days)

S5 - LF & VAS

LF (n.u.)

VAS

S6 - LF & VAS

LF (n.u.)

VAS

110

110

100

100

100

100

90

90

90

90

80

80

80

80

70

70

70

70

60

60

60

60

50

50

50

50

40

40

40

40

30

30

30

30

20

20

20

20

10

10

10

10

0
-10 0

10

11

12

13

14

0
15 -10

0
0

time (days)

Key:

10

11

12

time (days)

Phase A
HRV
Baseline
mean

Phase B
HRV

Exercise protocol
day six

2SD

VAS

Figure 4
Low Frequency HRV and VAS versus time.
Scatter plot representing five minutes of normalised LF HRV data collected between the hours of 1600
and 2000 over 14 days, with trend lines are added to Phase A and Phase B HRV data. Line graph
across days 6-14 representing VAS data collected pre-exercise, post-exercise, end of day six and every
12 hours from day 7-14. Baseline mean calculated from day 1-5 LF HRV data points. Four subjects
(S1, S2, S4, S5) have one LF HRV data point missing due to human error, and one data point excluded
due to ectopy exceeding 5%.

77

13

14

15

To summarise, the exercise protocol produced muscle failure in all six subjects, that
is, inability to perform one complete eccentric contraction. The exercise protocol also
increased the level of pain in all subjects, as evidenced by immediate post-exercise
pain intensity scores. Pain intensity scores for all subjects, except S4, declined by the
end of day six, although the rate of recovery varied between subjects. During the
expected DOMS period (day 7-9), the level of greatest pain intensity was variable
between subjects. During the recovery period (days 10-14), the DOMS recovery rate
was also variable as S1, S3 and S4 did not have a steady decline in pain intensity,
such as that seen in S2 and S6.

Using visual analysis, there was no correlation between the Phase B pain intensity
scores and changes to the normalised low and high frequency HRV parameters in the
six subjects tested. Although slight differences were observed in the stability of HRV
data and slope and level of trend line with some subjects, no consistent pattern of HF
or LF variation emerged that can be clearly attributed to DOMS. In conclusion, any
effect from DOMS on HRV was not visually identifiable from the results obtained at
the timeframes measured.

78

Discussion
The aim of this study was to determine whether the physiological effects of delayed
onset muscle soreness (DOMS), as a model of mild to moderate musculoskeletal pain,
would influence the autonomic nervous system (ANS) as measured by heart rate
variability (HRV). Heart rate data from six subjects was collected from baseline
through to the pre-DOMS period and from the DOMS period through to full recovery.
Pain intensity data was collected pre-exercise and immediate post-exercise, then
throughout the pre-DOMS, DOMS, and recovery periods. Delayed onset muscle
soreness occurred in 5 out of 6 subjects tested, as evidenced by pain intensity scores,
although visual assessment failed to reveal any consistent pattern between DOMS and
HRV. The results indicate that ANS changes did not occur after induction of DOMS
in the five subjects at the timeframes measured. Although ANS changes were
evident, as indicated by changes to HRV both before and after onset of DOMS, these
changes are more likely attributable to uncontrolled factors such as individual
physiological and environmental variation rather than DOMS.

Outcomes

Delayed onset muscle soreness as a model of pain

Pain is recognised to be a complex phenomenon involving both peripheral
mechanisms and higher centre involvement.37 The experience of pain can be
classified into sensory and affective dimensions, that is, physiological or
psychological elements.38 Delayed onset muscle soreness is an effective model of
pain in terms of the sensory dimension. For example, the mechanisms underlying
DOMS are purported to involve micro-damage to tissue and stimulation of free nerve
endings from the breakdown products of tissue damage,30 with a subsequent
inflammatory response involving substances such as bradykinin which are known to
stimulate free nerve endings.39 In terms of the affective or psychological dimension
of pain, DOMS would, like other noxious stimuli, be dependant upon aspects such as
cognitive appraisal of threat cues,40, 41 environmental context,42 coping strategies,43
and prevailing emotion (e.g. fear or anxiety).44 Previous studies have successfully

79

employed DOMS to examine the role of various affective components of pain, such as
fear of pain45 and the role of recalled, expected, and actual pain.46

The pain intensity scores in this study indicate that the exercise protocol was, for the
most part, effective in inducing DOMS, and that DOMS was an effective model of
pain. Completion of the exercise protocol was defined as the inability to perform one
complete eccentric contraction, at which point it was assumed that muscle failure was
achieved. Although the exercise protocol produced muscle failure in all subjects, the
protocol induced a pattern of pain in two subjects which was not a classic DOMS
pattern.17, 47 These two subjects (S1 and S5) appeared to have more upper-body
exercise in their routine physical activities than other subjects: S1 performed pull-ups
as part of a regular gym routine and S5 had a labour intensive occupation (winery
cellar-hand). Muscle failure was achieved in these subjects at the time of the exercise
intervention, yet, they reported less pain during the DOMS period (24-48 hours postexercise) than the immediate post-exercise period. The routine physical activities of
S1 and S5, coupled with the apparent minimal DOMS, suggests that the elbow and
forearm flexor muscles may have been more preconditioned due to the repeated-bout
effect. The repeated-bout effect occurs when subsequent bouts of eccentric exercise,
from 1-10 weeks after the initial bout, produce much less muscle damage implying
an adaptive and protective function.48, 49

Such preconditioning of S1 and S5 may have contributed to the apparently minimal

DOMS produced. Also of consideration, however, is that the reported intensity of
DOMS soreness has been found to have poor correlation with objective markers of
muscle damage.30, 50 Differences in reported DOMS intensity have been attributed to
factors such as natural variation in muscle stiffness and static flexibility,51 and genetic
differences in muscle fibre type and response to damage.52 This variation may
provide an explanation for the difference in reported DOMS pain intensity amongst
subjects of the current study, particularly S1 and S5. Although the manner in which
DOMS was induced was consistent with previous studies,16-18 DOMS may have been
more clearly established in all subjects with a more rigorous exercise protocol, such as
a dumbbell greater than 40-50% of the 1RM, or a protocol comprising both concentric
and eccentric exercise. Similarly, more thorough pre-screening of subjects may have

80

excluded candidates who were likely to be less susceptible to DOMS of the elbow and
forearm flexor muscles.

Heart rate variability

Independent of DOMS, the baseline high and low frequency HRV data showed intersubject differences. Some subjects recorded more stable HRV data than other
subjects did. Immediate post-exercise, pre-DOMS, DOMS, and recovery period data
also showed these inter-subject differences. For each subject, stability was variable
from baseline through to recovery, with apparent trends occurring in some cases but
this was prior to, rather than a result of, DOMS. Despite these observations, no
consistent pattern was evident that would suggest any correlation between HRV and
the reported pain associated with DOMS. The lack of consistent pattern highlights the
multitude of factors that are potentially involved when examining HRV data. When
methods of HRV analyses first emerged as a clinical tool, both researchers and
clinicians viewed it as a simple non-invasive technique to assess cardiovascular status.
Current literature is clear that data from HRV is more complex than originally
thought, as reflected in the rapidly evolving quantitative approaches to HRV, 29, 53-55
and the numerous investigations examining the overlapping linear and non-linear
factors that influence HRV. These influences include posture,56 mental stress,57
neuroendocrine and circadian processes,58, 59 respiration,26, 60 and ageing.61

In the present study, a pattern that would suggest a correlation between DOMS and
HRV would be a clear shift toward the HF parameter during the DOMS period (24-48
hours post-exercise). A shift towards HF would have indicated increased
parasympathetic activity in subjects during that timeframe.26, 32 By comparison, the
HRV in the same subjects without DOMS, would not display this pattern and only
show normal variation related to respiration and to processes such as circadian
rhythms62 or factors such as posture.63 This comparison is highly simplified however,
as the HRV of healthy subjects is remarkably complex,64 and caution should be
applied when interpreting all HRV data as it is dependent on factors such as age and
gender,65 serum lipoproteins and leukocytes,66 and lifestyle factors67 (for a
comprehensive account see the 1996 Task Force review).26 The results of the current

81

study do not appear to demonstrate a pattern that indicates a shift towards one or other
HRV parameter. Additionally, identification of proportional changes to HF and LF in
the present study was problematic due to difficulty representing five baseline data
points against 14 post-intervention data points.

The low frequency (LF) parameter of HRV represents both sympathetic and
parasympathetic activity to the heart.26 The high frequency (HF) parameter of HRV
represents parasympathetic activity mediated by the vagus nerve.26 As vagal activity
governs respiration, HF is also described as the respiratory frequency. The term
respiratory sinus arrhythmia (RSA) describes spontaneous fluctuations in heart rate
from respiratory-driven vagal modulation of sinoatrial node activity. These
fluctuations result from central coupling between respiratory oscillators in the
brainstem and autonomic outflow.31, 60, 68 Heart rate variability is largely dominated
by ANS activity, however, HRV is an indirect measure of mean autonomic tone.26
For example, HRV data reflects the state and function of the sinoatrial node, humoral
factors, and central heart rate oscillators such as the respiratory centre of the
brainstem.26 Autonomic activity, therefore, is not the sole influence on data obtained
from HRV. A more direct, yet invasive measure, such as microneurography, would
provide a more accurate representation of ANS activity on heart rate but was not
practical for this preliminary study.

Though HRV is an indirect measure of autonomic activity, any potential effect from
DOMS on the ANS may have been of insufficient magnitude to affect HRV. For
example, any change to local physiology from DOMS may have potentially caused
changes in local autonomic fibres, however these changes may have not been potent
enough to potentiate changes in autonomic fibres beyond the perturbed area. In this
type of scenario, any DOMS-induced ANS change would have negligible effect on
HRV.

82

Related research
Although there are no previous studies investigating the effect of DOMS on ANS
indices, there is related research that indicates a possible relationship between the
ANS and injured muscular or articular structures in humans. For instance, Grimm,
Cunningham, and Burke7 published a case series comparing ANS indices in acute
injured subjects and healthy controls. Grimm et al.7 concluded that skin conductance
was statistically greater in the musculoskeletal injury group than in the control group
and that analysis showed a highly significant positive relationship between skin
conductance and SBPLF [systolic blood pressure low frequency]. The greater skin
conductance and higher SBPLF in the acute injured group signifies increased activity
of cutaneous sympathetic neurons and increased activity of vasomotor sympathetic
neurons respectively. Grimm7 surmised that an interaction exists between cutaneous
and vasomotor sympathetic neurons in those with acute musculoskeletal injury, and
that this interaction manifested as altered cardiac and peripheral autonomic function.
Yet, Grimm7 found no difference in the low and high frequency variables between the
injured group and controls, despite the presence of smaller standard deviations in the
injury group.
Various limitations within the investigation by Grimm et al.7 highlight the need for
caution when interpreting their results. To illustrate, heterogeneity from age and sexmatched controls imparts a considerable amount of individual variation when
comparing ANS indices in the two groups. In addition, heterogeneity in the injured
group (e.g. site, duration, and intensity of injury), may have potentially introduced a
number of variables. These include psychological variables associated with low back
pain,69-71 physiological variables associated with density of pain sensitive free-nerve
endings in different tissues (e.g. the meniscotibial ligament of the knee versus the
medial collateral ligament of the knee),72, 73 or variables attributed to central
sensitisation mechanisms associated with injuries of longer duration (e.g. 24 hours
versus six days).74 In addition, it is possible that the routine chiropractic physical
examination given to the injured group and not the control group, biased Grimms7
results. For example, the spinal and cutaneous stimulation during the examination
may have influenced the ANS prior to data collection, although it is difficult to

83

predict how the stimulation would have manifested and how long such influence may
have persisted.

In the present study, the results do not clearly indicate that DOMS produced an effect
on the ANS via HRV. As autonomic activity and pain are highly complex and
individual, there may be a number of influences, both physiological and cognitive,
that may have been a factor in this study. The following section discusses these
influences.

Cognitive and physiological influences on the ANS and on pain

The study employed DOMS in an attempt to simulate a naturally occurring soft tissue
injury. It would be fair to assume that unlike DOMS, naturally occurring injuries are
not restricted to damage to one tissue type (e.g. myofascia), may be sudden in onset,
and may have a more threatening context overlaying the injury. Cognitive factors,
such as threat of harm or injury, can have a significant effect on the ANS.75, 76 In the
present study, cognitive factors may have a played a greater role than anticipated.
Research has shown that fear,75 threat value,76, 77 attention,78, 79 control,43
predictability,40, 41 information,41, 76, 80 environmental cues,81 emotion and context40, 44
all influence perception of pain and evocation of autonomic responses. Threat value
in particular has a profound effect on pain.40, 76, 77 Several features of the present
investigation provide examples of lack of threat. To illustrate, the DOMS information
sheet [see Appendix D] included information on the safety of DOMS. Recently, the
effect of safe and threatening cues in a situation involving a potential source of
pain (e.g. electric shock) has been found to have a considerable influence on
autonomic indices. Bradley, Silakowski, and Lang75 found that All subjects reacted
with greater defensive reactivity, including potentiated startle blinks, heightened skin
conductance, and cardiac deceleration in the context of threat, compared to safe,
cues. In the present study, the content of the DOMS information sheet may have
provided sufficient safe cues to subjects to reduce threat value. For example, the
impending discomfort was likened to soreness commonly encountered after overexertion, was described as short-lasting and not associated with damage to tissue other

84

than muscle, and was currently believed by researchers to confer a protective effect
due to muscle adaptation.

Inducing DOMS in the non-dominant arm, which is used less frequently in activities
of daily living, may have likewise reduced threat. By comparison, the investigation
by George, Dover, and Fillingim45 induced DOMS in the shoulder muscles of the
dominant arm, which may have been sufficiently threatening to subjects to generate
pain-related fear. This fear had a greater influence on pain perception and fear of
movement, than factors such as anxiety, gender, and catastrophising. Comparing the
present study to the Grimm et al.7 investigation, DOMS was a relatively homogeneous
tissue damage, which could have lessened threat value to subjects. Grimms data may
have been influenced by greater threat, as subjects had naturally occurring injuries
possibly involving heterogeneous tissue damage (e.g. knee injury, shoulder injury),
which may have also been acquired under more threatening circumstances.

Another cognitive aspect to consider in the present study is that previous experiences
of pain can affect the relationship between expected and actual pain responses.82
Dannecker, Price and Robinson46 have reported similar findings to several other
investigations83-86 in that the expectation of pain intensity and unpleasantness
correlated strongly with subsequent pain reports. Investigators are still elucidating the
relative influence of expectation and actual pain on recalled pain; however, it is
conceivable that in the present study, the recall of previous DOMS experiences may
have influenced the expectation of DOMS intensity, and thus pain report. The
influence of recalled, expected, and actual pain may have also played a role in the
Grimm et al.7 investigation, as a naturally acquired injury may have been more
painful, and possibly more threatening, with little or no previous experience of the
tissue damage (e.g. knee injury in a previously untraumatised knee).
Threat is strongly linked with context.40, 75, 87 The experimental environment of the
present study (gym and home) was familiar to subjects, and thus likely interpreted as
being safe. This contrasts with the unfamiliar private and thermo-controlled
autonomic laboratory of the Grimm et al.7 investigation, which may have influenced
ANS indices (e.g. greater skin conductance) more than the present study. The
experimental environment of the present study also included stimuli from a nature
85

documentary.25 Research has demonstrated that environmental factors such as

lighting, colour, and auditory stimuli,42 visual distraction,88-91 and exposure to scenic
imagery92-95 impact on patient recovery and pain thresholds and tolerance. Although
results differ in the literature, and the underlying mechanisms are not conclusive,
scenic, pleasant, and unpleasant visual stimuli affect autonomic indices.96-101 Based
on such research, it is reasonable to suppose that the visual and auditory stimuli
provided by the nature documentary, being distracting and scenic, might have
influenced the ANS and thus HRV during heart rate recording. The visual and
auditory stimuli may have also influenced respiratory rate, modulating RSA and thus
the HF parameter of HRV. Other studies using HRV have included controlled
breathing to restrict RSA.102-104 Due to the field nature of the present investigation, it
was not feasible to include controlled breathing during data collection.
A further element associated with threat is that of predictability.40 According to
Rhudy and Meagher,44 predictable yet unavoidable shock produces fear, which evokes
the release of endogenous opioids and attenuates pain. In contrast, the possibility of
shock results in apprehensive anticipation of a potential threat, which can facilitate
increased sensory receptivity and enhance pain.44 The anticipation of threat in the
absence of actual exposure is enough to potentiate startle reflexes and autonomic
responses.75 In the present study, it is possible that the anticipation of pain associated
with DOMS was lessened, as subjects were made aware of the temporal aspect of
DOMS during recruitment. Conversely, the pain associated with DOMS was also
predictable yet unavoidable, which too may have influenced pain perception and pain
report.

Aside from cognitive influences, normal physiological processes could have played a
greater role in the current study. Given that HRV is an indirect measure of the ANS,
the effect on HRV from processes such as circadian rhythms59, 62 and normal
hormonal fluctuation105 may have been of greater magnitude than an effect, if any,
from DOMS. To illustrate, baseline HRV data was very similar in some subjects to
the pre-DOMS and DOMS period data, indicating little overall fluctuation in HRV
from DOMS, even though small differences on certain days may have been evident.
Increased data point density, such as 10 minute Holter recordings taken hourly for 72
hours during the expected DOMS period, may have provided a more accurate
86

estimation of whether DOMS influenced HRV. This is a recommendation for any

future investigations.

The normal physiological response to the exercise protocol performed on day six may
have also played a role. Pober, Braun and Freedson106 have found that even a single
bout of exercise produced changes in HRV similar to that seen in studies on long-term
training. The authors suggest that the changes in autonomic function observed with a
single bout of exercise indicate a shift towards a more stable autonomic environment
for the heart. In the present study, this effect may have potentially been relevant to
the data, as HRV would shift toward HF after the exercise protocol with such an
effect. Unfortunately, however, it is uncertain how long any proposed effects on
HRV from a single bout of exercise might have persisted (e.g. immediate postexercise through to DOMS). Increased density of data points from the post-exercise
period through the DOMS period may have shown more clearly whether this effect
was relevant.

If the physiological changes associated with DOMS do have local or wider effects on
the ANS, the age and good health of the subjects may have compensated for any
potential changes. For example, it is reasonable to infer that the proposed
mechanisms underlying DOMS (micro-damage to muscle tissue and subsequent
inflammation) may have been less challenging to the physiology of a young healthy
subject than tissue damage that was more severe or heterogeneous. To illustrate, the
HRV of a young healthy person is likely more capable of compensating for any
physiological challenge than that of an older person, or one with limited
cardiovascular adaptability.107, 108 Such compensation may have been evident in one
subject of the present study (S4), who sustained a naturally-acquired injury during the
end of day six, the pre-DOMS period. No difference in the pre-DOMS and DOMS
period HRV was observed in this subject, possibly demonstrating the greater
compensation capacity present in a healthy young person.

87

Limitations and weaknesses

This study has several limitations and weaknesses. The design consisted of five
baseline HRV data points followed by nine post-intervention data points. Five
baseline data points is the minimum recommended in literature on single-subject
research designs.13, 15 A greater number of baseline HRV data points (minimum
eight) would have enhanced the ability to define the baseline and to evaluate any
changes observed after induction of DOMS, particularly proportional change of HRV
parameters. Greater frequency of measurement would have also benefited analysis of
the DOMS period (24-48 hours post-exercise). Increased frequency of heart rate
recording (e.g. Holter monitoring) during the DOMS period (days 7-9) would have
enhanced the ability to discern any effect of DOMS on the ANS, if any, as DOMS is
temporal and the effect on the ANS likely not persistent.

The ECG equipment (heart rate monitor) used in this study has shown good
reliability20 and validity.19 In contrast, the stability of short-term (5-15 minutes) HRV
recordings has shown highly variable reliability coefficients in several
investigations109-111 (for review see Sandercock et al.110), and the poor reliability of
HRV found in previous investigations may be a factor in this study. Another
limitation was that the recording environment of the present study was under limited
control, therefore influences on HRV from factors such as posture and head-tilt may
have been present during recording sessions.110, 112 Similarly, the field setting of the
study limited the ability to inspect and monitor ECG signal quality, or subjects
operation of the heart rate monitor. These factors may have contributed to the ectopy
experienced, despite attempts to control for similarity of recording conditions, time of
recording, and extrinsic influences such as stimulant consumption.

Pain intensity scores during baseline were not collected from subjects: subjects were
pain-free at recruitment and were assumed to remain pain-free throughout the baseline
period. This data may have been useful to compare baseline pain intensity with
baseline HRV. Nonetheless, repeated administration of a pain-related questionnaire
to pain-free subjects during the baseline period could conceivably have lead to
heightened somatic focus, and to higher retest scores. The term somatic focus
describes the tendency to attend to and report somatic symptoms, that is, physical

88

sensations, which do not correlate with objective measures of health status.113, 114
Correlations have been found between increased somatic focus and pain report in a
variety of populations, which potentially could include subjects of the current study.
These populations include younger age groups, those with history of abuse and
affective disorders, and those of lower socioeconomic status.115-118

Following convention on single-subject research designs, the current study used

visual analysis of results, such as trend, slope, and fluctuation.13-15 This method has
intrinsic strengths and weaknesses. Regarding intervention effects, some argue that
visual analysis emphasises clinical rather than statistical significance, has a low error
rate, and identifies treatment effects more conservatively.119-121 Yet, there are no
formal rules regarding interpretation of data and others contend that the poor
reliability of visual analysis weakens rigor and the ability to determine causality.119,
122, 123

Use of inferential statistical analysis may have been a beneficial adjunct in terms of
increased sensitivity towards interpreting any potential effect DOMS may have had
on HRV. However, like many single-subject designs, it is probable that the present
study failed to meet parametric assumptions (e.g. normality, equal variance, and serial
independence). Kazdin14 states that statistical analysis may be of value in singlesubject research when there is no stable baseline, the effects cannot be well predicted,
and statistical control may be required for extraneous factors in naturalistic
environments features which are evident in the current study. A number of authors
echo Kazdins sentiment, and spirited debate has occurred between proponents of
both visual and statistical analyses regarding sensitivity and what constitutes a
meaningful change, and in particular the phenomenon of autocorrelation.119, 120, 124-126
Autocorrelation is a statistical term referring to the correlation of a time series with its
own past and future values.119, 123 Such correlation complicates use of inferential
statistical analysis as it violates both parametric and non-parametric assumptions.
Statistical methods that do not account for any trend-related autocorrelation lowers
reliability by distorting effect size magnitude, confidence intervals, and p-values,
regardless of study design.119, 123, 124

89

For future investigations, measuring a variety of autonomic indices, such as HRV,

edge-light pupil cycle time, and galvanic skin response may be of benefit. Similarly,
larger sample sizes and a different design may also be advantageous. For example, a
prospective design using naturally occurring soft tissue injuries with similar
characteristics (e.g. site, intensity, duration) could be useful, although this design has
inherent logistical challenges. A cross-sectional design with matched controls may
also provide more robustness than the present study.

90

Conclusion
The results of this study indicate that changes to HRV did not occur as result of pain
associated with DOMS within the measurement timeframe employed. Although
slight differences in the stability of HRV data and slope of trend line occurred in some
subjects, no consistent pattern emerged that was attributable to DOMS. If DOMS was
able to influence the ANS, the effect on HRV appeared negligible. Furthermore,
changes to HRV parameters that were evident, were likely attributable to various
physiological and cognitive factors that are known to influence pain perception and
autonomic indices.

To date, the relationship between pain and the ANS has not been fully established: for
example, noxious stimuli clearly and consistently modulates autonomic activity3-5, 10
yet the autonomic effects from mild to moderate pain are less consistent.8, 10
Construction of this study was motivated by a tenet presented within many
osteopathic texts, namely, that musculoskeletal or visceral disturbance can have
effects elsewhere in the body via the ANS.1, 2, 127, 128 Scientific studies to date do not
support this osteopathic concept, and there is a scant amount of literature addressing
this issue.7 The results of the current study, whilst preliminary, did not provide
supportive evidence for this concept, and indeed may even challenge it. There have
been calls in the literature7 for a definitive illustration of whether musculoskeletal or
visceral disturbance could have a deleterious impact on the ANS, and potentially on
health and wellbeing. Establishing the nature and significance of these purported
links is important for evaluating tenets within osteopathy, and may be of clinical
relevance to those with acute injury, or those in chronic pain states.

91

Acknowledgments
Thanks are extended to Mr Darren Lyne for providing the nature documentary DVDs
used in this project.

92

References
1

2
3

5
6
7

10
11

12

13

14
15

16
17

DiGiovanna EL, Schiowitz S, Dowling DJ. An osteopathic approach to

diagnosis and treatment: 3rd Edition. Philadelphia: Lippincott, Williams &
Wilkins, 2005. p. 10-15.
Stone C. Science in the art of osteopathy: osteopathic principles and practice.
Cheltenham: Stanley Thornes Ltd, 1999. p. 28-56.
Adachi T, Meguro K, Sato A, Sato Y. Increases in cerebral blood flow
induced by nociceptive stimulation in ualothane-anesthetizen rats. Pain 1990;
41: S68.
Kaufman A, Sato A, Sato Y, Sugimoto H. Reflex changes in heart rate after
mechanical and thermal stimulation of the skin at various segmental levels in
cats. Neuroscience 1977; 2: 103-9.
Sato A, Schmidt RF. The modulation of visceral functions by somatic afferent
activity. Jpn J Physiol 1987; 37: 1-17.
Cortelli P, Pierangeli G. Chronic pain-autonomic interactions. Neurol Sci
2003; 24 Suppl 2: S68-70.
Grimm DR, Cunningham BM, Burke JR. Autonomic nervous system function
among individuals with acute musculoskeletal injury. J Manipulative Physiol
Ther 2005; 28: 44-51.
Sato A, Swenson RS. Sympathetic nervous system response to mechanical
stress of the spinal column in rats. J Manipulative Physiol Ther 1984; 7: 1417.
Budgell B, Hirano F. Innocuous mechanical stimulation of the neck and
alterations in heart-rate variability in healthy young adults. Auton Neurosci
2001; 91: 96-9.
Sato A, Sato Y, Schmidt RF. The impact of somatosensory input on autonomic
function. Heidelberg: Springer-Verlag, 1997.
Budgell B, Polus B. The effects of thoracic manipulation on heart rate
variability: a controlled crossover trial. J Manipulative Physiol Ther 2006; 29:
603-10.
Sterling M, Jull G, Wright A. Cervical mobilisation: concurrent effects on
pain, sympathetic nervous system activity and motor activity. Man Ther 2001;
6: 72-81.
Romeiser Logan L, Hickman RR, Harris SR, Heriza CB. Single-subject
research design: recommendations for levels of evidence and quality rating.
Dev Med Child Neurol 2008; 50: 99-103.
Kazdin AE. Single-case research designs: Methods for clinical and applied
settings. New York: Oxford University Press, 1982.
Backman CL, Harris SR. Case studies, single-subject research, and N of 1
randomized trials: comparisons and contrasts. Am J Phys Med Rehabil 1999;
78: 170-6.
Cleak MJ, Eston RG. Muscle soreness, swelling, stiffness and strength loss
after intense eccentric exercise. Br J Sports Med 1992; 26: 267-72.
Croisier JL, Camus G, Forthomme B, Maquet D, Vanderthommen M,
Crielaard JM. Delayed onset muscle soreness induced by eccentric isokinetic
exercise. Isokinet Exerc Sci 2003; 11: 21-9.

93

18

19

20

21
22

23

24

25
26

27

28

29

30
31
32
33

34

Graven-Nielsen T, Arendt-Nielsen L. Induction and assessment of muscle

pain, referred pain, and muscular hyperalgesia. Curr Pain Headache Rep
2003; 7: 443-51.
Gamelin FX, Berthoin S, Bosquet L. Validity of the polar S810 heart rate
monitor to measure R-R intervals at rest. Med Sci Sports Exerc 2006; 38: 88793.
Kingsley M, Lewis MJ, Marson RE. Comparison of Polar 810s and an
ambulatory ECG system for RR interval measurement during progressive
exercise. Int J Sports Med 2005; 26: 39-44.
Melzack R. The short-form McGill pain questionnaire. Pain 1987; 30: 191-7.
Grafton KV, Foster NE, Wright CC. Test-retest reliability of the short-form
McGill pain questionnaire: assessment of intraclass correlation coefficients
and limits of agreement in patients with osteoarthritis. Clin J Pain 2005; 21:
73-82.
Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual
analogue scales as ratio scale measures for chronic and experimental pain.
Pain 1983; 17: 45-56.
de Boer AG, van Lanschot JJ, Stalmeier PF, van Sandick JW, Hulscher JB, de
Haes JC, Sprangers MA. Is a single-item visual analogue scale as valid,
reliable and responsive as multi-item scales in measuring quality of life? Qual
Life Res 2004; 13: 311-20.
Attenborough DF. The living planet - a portrait of the earth: British
Broadcasting Corporation (BBC), 1984.
Task Force of the European Society of Cardiology and the North American
Society of Pacing and Electrophysiology. Heart rate variability: standards of
measurement, physiological interpretation and clinical use. Circulation 1996;
93: 1043-65.
Kamen PW, Tonkin AM. Application of the Poincare plot to heart rate
variability: a new measure of functional status in heart failure. Aust N Z J Med
1995; 25: 18-26.
Kamen PW, Krum H, Tonkin AM. Poincare plot of heart rate variability
allows quantitative display of parasympathetic nervous activity in humans.
Clin Sci (Lond) 1996; 91: 201-8.
Brennan M, Palaniswami M, Kamen P. Do existing measures of Poincare plot
geometry reflect nonlinear features of heart rate variability? IEEE Trans
Biomed Eng 2001; 48: 1342-7.
Friden J, Lieber RL. Eccentric exercise-induced injuries to contractile and
cytoskeletal muscle fibre components. Acta Physiol Scand 2001; 171: 321-6.
Stauss HM. Heart rate variability. Am J Physiol Regul Integr Comp Physiol
2003; 285: R927-31.
Stein PK, Kleiger RE. Insights from the study of heart rate variability. Annu
Rev Med 1999; 50: 249-61.
Zhong Y, Jan KM, Ju KH, Chon KH. Quantifying cardiac sympathetic and
parasympathetic nervous activities using principal dynamic modes analysis of
heart rate variability. Am J Physiol Heart Circ Physiol 2006; 291: H1475-83.
Sleight P, La Rovere MT, Mortara A, Pinna G, Maestri R, Leuzzi S, Bianchini
B, Tavazzi L, Bernardi L. Physiology and pathophysiology of heart rate and
blood pressure variability in humans: is power spectral analysis largely an
index of baroreflex gain? Clin Sci (Lond) 1995; 88: 103-9.

94

35

36

37

38
39
40

41

42

43

44
45

46

47
48

49
50

51

52

Montano N, Gnecchi-Ruscone T, Porta A, Lombardi F, Malliani A, Barman

SM. Presence of vasomotor and respiratory rhythms in the discharge of single
medullary neurons involved in the regulation of cardiovascular system. J
Auton Nerv Syst 1996; 57: 116-22.
Cooley RL, Montano N, Cogliati C, van de Borne P, Richenbacher W, Oren
R, Somers VK. Evidence for a central origin of the low-frequency oscillation
in RR-interval variability. Circulation 1998; 98: 556-61.
Merskey H, Bogduk N. Classification of chronic pain: descriptions of chronic
pain syndromes and definitions of pain terms: 2nd Edition. Seattle: IASP Press
1994.
Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965; 150:
971-9.
Lieber RL, Friden J. Morphologic and mechanical basis of delayed-onset
muscle soreness. J Am Acad Orthop Surg 2002; 10: 67-73.
Moseley GL, Brhyn L, Ilowiecki M, Solstad K, Hodges PW. The threat of
predictable and unpredictable pain: differential effects on central nervous
system processing? Aust J Physiother 2003; 49: 263-7.
Jackson T, Pope L, Nagasaka T, Fritch A, Iezzi T, Chen H. The impact of
threatening information about pain on coping and pain tolerance. Br J Health
Psychol 2005; 10: 441-51.
Malenbaum S, Keefe FJ, Williams AC, Ulrich R, Somers TJ. Pain in its
environmental context: implications for designing environments to enhance
pain control. Pain 2008; 134: 241-4.
Crombez G, Eccleston C, De Vlieger P, Van Damme S, De Clercq A. Is it
better to have controlled and lost than never to have controlled at all? An
experimental investigation of control over pain. Pain 2008; 137: 631-9.
Rhudy JL, Meagher MW. Fear and anxiety: divergent effects on human pain
thresholds. Pain 2000; 84: 65-75.
George SZ, Dover GC, Fillingim RB. Fear of pain influences outcomes after
exercise-induced delayed onset muscle soreness at the shoulder. Clin J Pain
2007; 23: 76-84.
Dannecker EA, Price DD, Robinson ME. An examination of the relationships
among recalled, expected, and actual intensity and unpleasantness of delayed
onset muscle pain. J Pain 2003; 4: 74-81.
Cleak MJ, Eston RG. Delayed onset muscle soreness: mechanisms and
management. J Sports Sci 1992; 10: 325-41.
McHugh MP. Recent advances in the understanding of the repeated bout
effect: the protective effect against muscle damage from a single bout of
eccentric exercise. Scand J Med Sci Sports 2003; 13: 88-97.
Nosaka K, Clarkson PM. Muscle damage following repeated bouts of high
force eccentric exercise. Med Sci Sports Exerc 1995; 27: 1263-9.
Newham DJ. The consequences of eccentric contractions and their relationship
to delayed onset muscle pain. Eur J Appl Physiol Occup Physiol 1988; 57:
353-9.
McHugh MP, Connolly DA, Eston RG, Kremenic IJ, Nicholas SJ, Gleim GW.
The role of passive muscle stiffness in symptoms of exercise-induced muscle
damage. Am J Sports Med 1999; 27: 594-9.
Ebbeling CB, Clarkson PM. Exercise-induced muscle damage and adaptation.
Sports Med 1989; 7: 207-34.

95

53

54

55

56

57

58

59

60
61

62

63

64
65

66

67

Belova NY, Mihaylov SV, Piryova BG. Wavelet transform: A better approach
for the evaluation of instantaneous changes in heart rate variability. Auton
Neurosci 2007; 131: 107-22.
Radespiel-Troger M, Rauh R, Mahlke C, Gottschalk T, Muck-Weymann M.
Agreement of two different methods for measurement of heart rate variability.
Clin Auton Res 2003; 13: 99-102.
Guzzetti S, Borroni E, Garbelli PE, Ceriani E, Della Bella P, Montano N,
Cogliati C, Somers VK, Malliani A, Porta A. Symbolic dynamics of heart rate
variability: a probe to investigate cardiac autonomic modulation. Circulation
2005; 112: 465-70.
Montano N, Ruscone TG, Porta A, Lombardi F, Pagani M, Malliani A. Power
spectrum analysis of heart rate variability to assess the changes in
sympathovagal balance during graded orthostatic tilt. Circulation 1994; 90:
1826-31.
Terkelsen AJ, Andersen OK, Molgaard H, Hansen J, Jensen TS. Mental stress
inhibits pain perception and heart rate variability but not a nociceptive
withdrawal reflex. Acta Physiol Scand 2004; 180: 405-14.
Molgaard H, Sorensen KE, Bjerregaard P. Circadian variation and influence of
risk factors on heart rate variability in healthy subjects. Am J Cardiol 1991;
68: 777-84.
Scheer FA, Van Doornen LJ, Buijs RM. Light and diurnal cycle affect
autonomic cardiac balance in human; possible role for the biological clock.
Auton Neurosci 2004; 110: 44-8.
Yasuma F, Hayano J. Respiratory sinus arrhythmia: why does the heartbeat
synchronize with respiratory rhythm? Chest 2004; 125: 683-90.
Jensen-Urstad K, Storck N, Bouvier F, Ericson M, Lindblad LE, JensenUrstad M. Heart rate variability in healthy subjects is related to age and
gender. Acta Physiol Scand 1997; 160: 235-41.
Bonnemeier H, Richardt G, Potratz J, Wiegand UK, Brandes A, Kluge N,
Katus HA. Circadian profile of cardiac autonomic nervous modulation in
healthy subjects: differing effects of aging and gender on heart rate variability.
J Cardiovasc Electrophysiol 2003; 14: 791-9.
Yamanaka Y, Honma K. Cardiovascular autonomic nervous response to
postural change in 610 healthy Japanese subjects in relation to age. Auton
Neurosci 2006; 124: 125-31.
Goldberger AL. Non-linear dynamics for clinicians: chaos theory, fractals, and
complexity at the bedside. Lancet 1996; 347: 1312-4.
Agelink MW, Malessa R, Baumann B, Majewski T, Akila F, Zeit T, Ziegler
D. Standardized tests of heart rate variability: normal ranges obtained from
309 healthy humans, and effects of age, gender, and heart rate. Clin Auton Res
2001; 11: 99-108.
Jensen-Urstad M, Jensen-Urstad K, Ericson M, Johansson J. Heart rate
variability is related to leucocyte count in men and to blood lipoproteins in
women in a healthy population of 35-year-old subjects. J Intern Med 1998;
243: 33-40.
Thayer JF, Hall M, Sollers JJ, 3rd, Fischer JE. Alcohol use, urinary cortisol,
and heart rate variability in apparently healthy men: evidence for impaired
inhibitory control of the HPA axis in heavy drinkers. Int J Psychophysiol
2006; 59: 244-50.

96

68
69

70

71
72
73

74
75
76

77

78
79

80

81
82
83

84
85

86

Sztajzel J. Heart rate variability: a noninvasive electrocardiographic method to

measure the autonomic nervous system. Swiss Med Wkly 2004; 134: 514-22.
Pincus T, Burton AK, Vogel S, Field AP. A systematic review of
psychological factors as predictors of chronicity/disability in prospective
cohorts of low back pain. Spine 2002; 27: E109-20.
Hoogendoorn WE, van Poppel MN, Bongers PM, Koes BW, Bouter LM.
Systematic review of psychosocial factors at work and private life as risk
factors for back pain. Spine 2000; 25: 2114-25.
Bogduk N. Psychology and low back pain. Int J Osteopath Med 2006; 9: 4953.
Zimny ML. Mechanoreceptors in articular tissues. Am J Anat 1988; 182: 1632.
Biedert R, Lobenhoffer P, Lattermann C, Stauffer E, Muller W. Free nerve
endings in the medial and posteromedial capsuloligamentous complexes:
occurrence and distribution. Knee Surg Sports Traumatol Arthrosc 2000; 8:
68-72.
Siddall PJ, Cousins MJ. Spinal pain mechanisms. Spine 1997; 22: 98-104.
Bradley MM, Silakowski T, Lang PJ. Fear of pain and defensive activation.
Pain 2008; 137: 156-63.
Boston A, Sharpe L. The role of threat-expectancy in acute pain: effects on
attentional bias, coping strategy effectiveness and response to pain. Pain 2005;
119: 168-75.
Van Damme S, Crombez G, Van Nieuwenborgh-De Wever K, Goubert L. Is
distraction less effective when pain is threatening? An experimental
investigation with the cold pressor task. Eur J Pain 2008; 12: 60-7.
Miron D, Duncan GH, Bushnell MC. Effects of attention on the intensity and
unpleasantness of thermal pain. Pain 1989; 39: 345-52.
Keogh E, Hatton K, Ellery D. Avoidance versus focused attention and the
perception of pain: differential effects for men and women. Pain 2000; 85:
225-30.
Watt-Watson J, Stevens B, Katz J, Costello J, Reid GJ, David T. Impact of
preoperative education on pain outcomes after coronary artery bypass graft
surgery. Pain 2004; 109: 73-85.
Bayer TL, Baer PE, Early C. Situational and psychophysiological factors in
psychologically induced pain. Pain 1991; 44: 45-50.
Crombez G, Eccleston C, Baeyens F, Eelen P. The disruptive nature of pain:
an experimental investigation. Behav Res Ther 1996; 34: 911-8.
Crombez G, Vervaet L, Baeyens F, Lysens R, Eelen P. Do pain expectancies
cause pain in chronic low back patients? A clinical investigation. Behav Res
Ther 1996; 34: 919-25.
Arntz A, van Eck M, Heijmans M. Predictions of dental pain: the fear of any
expected evil, is worse than the evil itself. Behav Res Ther 1990; 28: 29-41.
Wallace LM. Surgical patients' expectations of pain and discomfort: does
accuracy of expectations minimise post-surgical pain and distress? Pain 1985;
22: 363-73.
Arntz A, van den Hout MA, van den Berg G, Meijboom A. The effects of
incorrect pain expectations on acquired fear and pain responses. Behav Res
Ther 1991; 29: 547-60.

97

87

88

89

90

91
92

93
94

95
96
97
98
99
100

101

102

103

104

Munafo MR, Stevenson J. Selective processing of threat-related cues in day

surgery patients and prediction of post-operative pain. Br J Health Psychol
2003; 8: 439-49.
Wolitzky K, Fivush R, Zimand E, Hodges L, Rothbaum BO. Effectiveness of
virtual reality distraction during a painful medical procedure in pediatric
oncology patients. Psychol Health 2005; 6: 817-24.
Lee DW, Chan AC, Wong SK, Fung TM, Li AC, Chan SK, Mui LM, Ng EK,
Chung SC. Can visual distraction decrease the dose of patient-controlled
sedation required during colonoscopy? A prospective randomized controlled
trial. Endoscopy 2004; 36: 197-201.
Hoffman HG, Patterson DR, Carrougher GJ. Use of virtual reality for
adjunctive treatment of adult burn pain during physical therapy: a controlled
study. Clin J Pain 2000; 16: 244-50.
Miller AC, Hickman LC, Lemasters GK. A distraction technique for control of
burn pain. J Burn Care Rehabil 1992; 13: 576-80.
Diette GB, Lechtzin N, Haponik E, Devrotes A, Rubin HR. Distraction
therapy with nature sights and sounds reduces pain during flexible
bronchoscopy: a complementary approach to routine analgesia. Chest 2003;
123: 941-8.
Ulrich RS. View through a window may influence recovery from surgery.
Science 1984; 224: 420-1.
Ulrich RS, Lunden O, Etinge JL. Effects of exposure to nature and abstract
pictures on patients recovery from heart surgery. Psychophysiology 1993; 30:
S1-7.
Tse MM, Ng JK, Chung JW, Wong TK. The effect of visual stimuli on pain
threshold and tolerance. J Clin Nurs 2002; 11: 462-9.
Steele K, Cox T. Psychological and physiological reactions to visual
representations of war. Int J Psychophysiol 1986; 3: 237-52.
Jonsson P, Hansson-Sandsten M. Respiratory sinus arrhythmia in response to
fear-relevant and fear-irrelevant stimuli. Scand J Psychol 2008; 49: 123-31.
Dimberg U. Facial reactions to fear-relevant and fear-irrelevant stimuli. Biol
Psychol 1986; 23: 153-61.
Wittling W, Block A, Genzel S, Schweiger E. Hemisphere asymmetry in
parasympathetic control of the heart. Neuropsychologia 1998; 36: 461-8.
Frazier TW, Strauss ME, Steinhauer SR. Respiratory sinus arrhythmia as an
index of emotional response in young adults. Psychophysiology 2004; 41: 7583.
Palomba D, Sarlo M, Angrilli A, Mini A, Stegagno L. Cardiac responses
associated with affective processing of unpleasant film stimuli. Int J
Psychophysiol 2000; 36: 45-57.
La Rovere MT, Pinna GD, Maestri R, Mortara A, Capomolla S, Febo O,
Ferrari R, Franchini M, Gnemmi M, Opasich C, Riccardi PG, Traversi E,
Cobelli F. Short-term heart rate variability strongly predicts sudden cardiac
death in chronic heart failure patients. Circulation 2003; 107: 565-70.
Radaelli A, Raco R, Perfetti P, Viola A, Azzellino A, Signorini MG, Ferrari
AU. Effects of slow, controlled breathing on baroreceptor control of heart rate
and blood pressure in healthy men. J Hypertens 2004; 22: 1361-70.
Halamek J, Kara T, Jurak P, Soucek M, Francis DP, Davies LC, Shen WK,
Coats AJ, Novak M, Novakova Z, Panovsky R, Toman J, Sumbera J, Somers
VK. Variability of phase shift between blood pressure and heart rate

98

105

106
107
108

109

110
111

112

113

114
115

116

117
118
119

120

121

122

fluctuations: a marker of short-term circulation control. Circulation 2003; 108:

292-7.
Buijs RM, van Eden CG, Goncharuk VD, Kalsbeek A. The biological clock
tunes the organs of the body: timing by hormones and the autonomic nervous
system. J Endocrinol 2003; 177: 17-26.
Pober DM, Braun B, Freedson PS. Effects of a single bout of exercise on
resting heart rate variability. Med Sci Sports Exerc 2004; 36: 1140-8.
Acharya UR, Kannathal N, Sing OW, Ping LY, Chua T. Heart rate analysis in
normal subjects of various age groups. Biomed Eng Online 2004; 3: 24.
Sagiv M, Ben-Sira D, Rudoy J. Cardiovascular response during upright
isometric dead lift in young, older, and elderly healthy men. Int J Sports Med
1988; 9: 134-6.
Kleiger RE, Bigger JT, Bosner MS, Chung MK, Cook JR, Rolnitzky LM,
Steinman R, Fleiss JL. Stability over time of variables measuring heart rate
variability in normal subjects. Am J Cardiol 1991; 68: 626-30.
Sandercock GR, Bromley PD, Brodie DA. The reliability of short-term
measurements of heart rate variability. Int J Cardiol 2005; 103: 238-47.
Tarkiainen TH, Timonen KL, Tiittanen P, Hartikainen JE, Pekkanen J, Hoek
G, Ibald-Mulli A, Vanninen EJ. Stability over time of short-term heart rate
variability. Clin Auton Res 2005; 15: 394-9.
Pitzalis MV, Mastropasqua F, Massari F, Forleo C, Di Maggio M, Passantino
A, Colombo R, Di Biase M, Rizzon P. Short- and long-term reproducibility of
time and frequency domain heart rate variability measurements in normal
subjects. Cardiovasc Res 1996; 32: 226-33.
O'Brien EM, Atchison JW, Gremillion HA, Waxenberg LB, Robinson ME.
Somatic focus/awareness: relationship to negative affect and pain in chronic
pain patients. Eur J Pain 2008; 12: 104-15.
Watson D, Pennebaker JW. Health complaints, stress, and distress: exploring
the central role of negative affectivity. Psychol Rev 1989; 96: 234-54.
Geisser ME, Gaskin ME, Robinson ME, Greene AF. The relationship of
depression and somatic focus to experimental and clinical pain in chronic pain
patients. Psychol Health 1993; 8: 405-15.
Campbell LC, Riley JL, 3rd, Kashikar-Zuck S, Gremillion H, Robinson ME.
Somatic, affective, and pain characteristics of chronic TMD patients with
sexual versus physical abuse histories. J Orofac Pain 2000; 14: 112-9.
Riley JL, 3rd, Robinson ME, Kvaal SA, Gremillion HA. Effects of physical
and sexual abuse in facial pain: direct or mediated? Cranio 1998; 16: 259-66.
Nimnuan C, Hotopf M, Wessely S. Medically unexplained symptoms: an
epidemiological study in seven specialities. J Psychosom Res 2001; 51: 361-7.
Brossart DF, Parker RI, Olson EA, Mahadevan L. The relationship between
visual analysis and five statistical analyses in a simple AB single-case research
design. Behav Modif 2006; 30: 531-63.
Bobrovitz CD, Ottenbacher KJ. Comparison of visual inspection and statistical
analysis of single-subject data in rehabilitation research. Am J Phys Med
Rehabil 1998; 77: 94-102.
Parsonson BS, Baer DM. The visual analysis of data, and current research
into the stimuli controlling it. In: Kratochwill TR, Levin JR, eds. Single-case
research design and analysis. Hillsdale: Lawrence Erlbaum, 1992; 15-40.
Harbst KB, Ottenbacher KJ, Harris SR. Interrater reliability of therapists'
judgements of graphed data. Phys Ther 1991; 71: 107-15.

99

123
124
125
126

127
128

Parker RI. Increased reliability for single-case research results: is the bootstrap
the answer? Behav Ther 2006; 37: 326-38.
Parker RI, Hagan-Burke S. Useful effect size interpretations for single case
research. Behav Ther 2007; 38: 95-105.
Nourbakhsh MR, Ottenbacher KJ. The statistical analysis of single-subject
data: a comparative examination. Phys Ther 1994; 74: 768-76.
Matyas TA, Greenwood KM. Visual analysis of single-case time series:
effects of variability, serial dependence, and magnitude of intervention effects.
J Appl Behav Anal 1990; 23: 341-51.
Kuchera ML, Kuchera WA. Osteopathic principles in practice: 2nd Edition.
Columbus: Greyden Press, 1993. p. 7-12.
Parsons J, Marcer N. Osteopathy: models for diagnosis, treatment and
practice. London: Churchill Livingstone, 2006. p. 107-35.

100

Appendix A: Subject consent form

CONSENT FORM

Muscle Soreness and Heart Rate Project

This research project investigates the effects of muscle soreness on heart rate. The research is being undertaken
by Larissa Morgan from Unitec New Zealand, and will be supervised by Robert Moran and Dr Craig Hilton.
Name of Subject:.
I have seen the Information Sheets dated .for people taking part in the
Muscle Soreness and Heart Rate Project. I have had the opportunity to read the contents of the two information
sheets and to discuss the project with the researchers and I am satisfied with the explanations I have been given.
I understand that taking part in this project is voluntary (my choice) and that I may withdraw from the project
any time up until the point of data analysis (1 week after the last day of scheduled data collection) and this will
in no way affect my access to the services provided by Unitec New Zealand or any other support service.
I understand that I can withdraw from the research if, for any reason, I want this.
I understand that my participation in this project is confidential and that no material that could identify me will
be used in any reports on this project.
I have had enough time to consider whether I want to take part.
I know whom to contact if I have any questions or concerns about the project.
The principal researcher is Larissa Morgan [ph: () , e-mail:
morgal02@studentmail.unitec.ac.nz]
Signature.subject ..........(date)
Project explained by
Signature.

..........(date)

This study has been approved by the Unitec Research Ethics Committee from 26 July 2006 to 31 December 2007. If you have any
complaints or reservations about the ethical conduct of this research, you may contact the Committee through the Chairperson (ph: 09
815-4321 ext 8384). Any issues you raise will be treated in confidence and investigated fully, and you will be informed of the outcome

101

Appendix B: Subject information sheet

INFORMATION SHEET

Muscle Soreness and Heart Rate Project

About this research
You are invited to take part in a research project being undertaken as part of the completion
requirements of a Masters of Osteopathy degree.
This research investigates the effects of eccentric exercise of the non-dominant arm on nerve activity
(namely heart rate) in males aged 18-40.

Participation in this project will require:

Signing a consent form

Attendance at an initial screening appointment for collection of health information (e.g.

smoking history, age, and spinal/cardiac/respiratory or neurological problems, disease or
history of surgery) to establish your suitability for participation in the research.

Removal of your shirt and placement of a chest strap and wristwatch (this will be loaned to
you to record heart rate). The use of the watch will be fully demonstrated to you. In the
experiment you will set these up for yourself. The researchers will be available by phone to
assist you with setting these up if you experience any technical problems.

Demonstrate that you can confidently operate the watch and correctly locate the chest strap.

Demonstrate comprehension of daily protocol for data collection.

Setting aside a consistent time in the same venue (e.g. home) for 14 consecutive days, for 15
minutes each day at a time specified. During this time you will need to wear the heart rate
monitor and transmitter chest strap, while watching a nature documentary that will be
provided to you on DVD or videotape.

Being available to attend Unitec for 30 minutes to perform an exercise protocol on Day 6 of
data collection that will induce muscle soreness (see attached Information Sheet).

Consent to the research teams use of research data in preparing both a research project
dissertation and an article for publication (all data will be anonymised)
Your involvement in this research will aid the understanding of the human bodys response to
eccentric exercise.

The Researchers
The primary researcher is Larissa Morgan
This project is being supervised by Robert Moran and Dr Craig Hilton

102

Participation and Consent

We would greatly appreciate your participation in the study. If you would like to participate please
complete a consent form for this project and return it to Larissa Morgan.

You have the right to not participate. If you consent but later wish to withdraw from this
research, you may do so at any time up until the point of data analysis (1 week after the last day
of scheduled data collection). This can be done by phoning us, or by telling us when we contact
you that you do not want to participate.
Getting help
Please contact either one of us should you require help with anything regarding this research project.
Larissa Morgan E-mail morgal02@studentmail.unitec.ac.nz
Ph
Robert Moran

()

E-mail rmoran@unitec.ac.nz
Ph
(09) 815 4321 x8642

Dr Craig Hilton E-mail chilton@unitec.ac.nz

Ph
(09) 815 4321 x8601
Information and concerns
If you want further information about the project you can call, or email the above address.
At anytime if you are concerned or confused about the research project you may contact Larissa
Morgan the primary researcher using the contact details above.

If you have concerns about the way in which the research is being conducted you can contact the
following:
Health Advocates: Advocates Network Services Trust, Phone (09) 623 5799, 0800 205 555, Fax (09)
623 5798, PO Box 9983, Newmarket, Auckland.
Confidentiality
Confidentiality and your anonymity will be protected in the following ways:
o

Information and data collected from you during the research will be labelled with an
identification number for the sole purpose of anonymously comparing your data between
subsequent sessions.

All computer records will be accessible only by passwords held only by the researchers.

Any data derived from the research will be anonymised and your identity will be kept
confidential.

A copy of the final report will be available at Unitec New Zealand library. All subjects are welcome to
view this. Summaries and recommendations may be published in research journals.
Finally, we would like to thank you for your valuable contribution to this research.
This study has been approved by the UnitecResearch Ethics Committee from 26 July 2006 to 31 December 2007. If you have
any complaints or reservations about the ethical conduct of this research, you may contact the Committee through the
Chairperson (ph: 09 815-4321 ext 8384). Any issues you raise will be treated in confidence and investigated fully, and you will
be informed of the outcome

103

Appendix C: Operational instructions

Instructions for Heart Rate Recording

Please remember: no caffeine, alcohol, food or exercise 3 hours prior to recording. Caffeine is found
in coffee, tea, and energy drinks with guarana such as red bull, V, lift plus, e2.
Familiarise yourself with the instructions for the first couple of days
CHEST STRAP TRANSMITTER
1. Moisten the 2 electrode areas at each end of the strap under running water, and make sure they
are well moistened.
2. Position the letter L on the plastic connector with the word LEFT on the strap, and fasten.
3. Loop the strap around your chest (under your clothes) and position against your skin - fasten
the RIGHT side of the strap to the plastic connector
4. Adjust the strap length so that it fits snugly yet comfortably
5. Position the plastic connector at the centre of the lower end of your sternum (breast bone). The
strap should be just below your pectoral muscles and the connector in a central and upright
position.
6. Check that the wet electrode areas are firmly against your skin
7. Put wristwatch on
PREPARE TO WATCH THE DVD
1. Remove the potential for distractions, i.e. telephones & mobiles, pets, T.V., music/radio,
children.
2. No food or drink is to be taken at this time
3. Insert the DVD and position yourself comfortably in a chair (use the same chair and same
seated position each day)
4. Make sure wristwatch is less than 1 metre from the chest transmitter
5. Once the documentary begins, wait approximately 2 minutes before starting heart rate
recording
HEART RATE RECORDING USING THE WRISTWATCH
1. Press the red start button
2. The wristwatch will search for the transmission from the chest strap
3. Once the transmission is found the watch will display a beating heart icon
4. Press the red start button again to begin recording, a stop-watch timer will now display
5. Watch the DVD for approximately 15 minutes, keeping movement to a minimum
6. Press the stop button (lower left on watch) to stop recording
7. Press the stop button again to return the watch back to normal time and date display. Please
note: your heart rate and other physiological data cannot be accessed from the wristwatch
itself without the appropriate software and uplink unit.
8. Unfasten the chest strap transmitter and remove the plastic connector from both ends of the
strap
9. Store the strap, connector, and watch in the separate bags provided to prevent moisture from
affecting the components.
10. Fill in the diary/comments sheet noting any stressful incidents, accidents, injuries, or illnesses
that may have occurred or been present that day, or any necessary medication that may have
been taken during the day.

104

Appendix D: DOMS information sheet

INFORMATION SHEET

Delayed Onset Muscle Soreness

What is delayed onset muscle soreness?
Delayed onset muscle soreness (DOMS) is the sensation of dull aching pain and discomfort felt in the
muscles after having done unaccustomed or strenuous exercise.

Why does DOMS come about?

DOMS particularly occurs after having done exercise that involved the muscles lengthening whilst
trying to resist or control a load otherwise known as an eccentric contraction. An example of
eccentric contraction is found in walking down hill: the quadriceps muscle contracts to control the rate
of knee flexion against gravity as we step down the slope, and lengthens during the process. Another
similar example is found in straightening a bent arm when holding a heavy shopping bag: the biceps is
lengthening whilst controlling the rate of lowering the bag.

When do I feel DOMS?

One of the key features of DOMS is, as the term implies, the delayed onset of discomfort. There is no
discomfort immediately after the exercise or activity as DOMS typically develops several hours
afterwards, peaking 24-48 hours later and disappearing completely by 3-7 days. The time frame of
DOMS distinguishes it from temporary soreness which is experienced during the final stages of muscle
fatigue and which is thought to be caused by metabolic waste accumulation (e.g. lactic acid).

How does DOMS happen?

The precise physiological mechanism behind DOMS is not yet fully understood, however there are
currently two well-established and accepted theories:
1. the loading on the muscle from the eccentric contraction disrupts and strains microscopic
components of the muscle
2. a subsequent inflammatory reaction to the cellular disruption

Will DOMS affect other tissues in the body?

No. DOMS only involves muscle and is not associated with damage to blood vessels, nerves, bones,
joints, ligaments, or organs.
The disruption to muscle is not permanent and there is a rapid and complete resolution of discomfort.
Recent research findings suggest that DOMS has an adaptive and protective role in the body as
subsequent bouts of eccentric exercise produce much less soreness than previous bouts.

105

Appendix E: International Journal of Osteopathic

Medicine Guide for Authors
The journal Editors welcome contributions for publication from the following categories: Letters to the
Editor, Reviews and Original Articles, Commentaries and Clinical Practice case studies with
educational value.
Online Submission
Submission to this journal proceeds totally online.(http://ees.elsevier.com/ijom) you will be guided
stepwise through the creation and uploading of the various files. The system automatically converts
source files to a single Adobe Acrobat PDF version of the article, which is used in the peer-review
process. Please note that even though manuscript source files are converted to PDF at submission for
the review process, these source files are needed for further processing after acceptance. All
correspondence, including notification of the Editor's decision and requests for revision, takes place by
e-mail and via the Author's homepage, removing the need for a hard-copy paper trail.
The above represents a very brief outline of this form of submission. It can be advantageous to print
this "Guide for Authors" section from the site for reference in the subsequent stages of article
preparation.
Submission of an article implies that the work described has not been published previously (except in
the form of an abstract or as part of a published lecture or academic thesis), that it is not under
consideration for publication elsewhere, that its publication is approved by all authors and tacitly or
explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will
not be published elsewhere in the same form, in English or in any other language, without the written
consent of the Publisher.
Types of contributions
Letters to the Editor As is common in biomedical journals the editorial board welcomes critical
response to any aspect of the journal. In particular, letters that point out deficiencies and that add to, or
further clarify points made in a recently published work, are welcomed. The Editorial Board reserves
the right to offer authors of papers the right of rebuttal, which may be published alongside the letter.
Reviews and Original Articles These should be either i) reports of new findings related to osteopathic
medicine that are supported by research evidence. These should be original, previously unpublished
works. The report will normally be divided into the following sections: abstract, introduction, materials
and methods, results, discussion, conclusion, references. Or ii) critical or systematic review that seeks
to summarise or draw conclusions from the established literature on a topic relevant to osteopathic
medicine.
Short review The drawing together of present knowledge in a subject area, in order to provide a
background for the reader not currently versed in the literature of a particular topic. Shorter in length
than and not intended to be as comprehensive as that of the literature review paper. With more
emphasis on outlining areas of deficit in the current literature that warrant further investigation.
Research Note Findings of interest arising from a larger study but not the primary aim of the research
endeavour, for example short experiments aimed at establishing the reliability of new equipment used
in the primary experiment or other incidental findings of interest, arising from, but not the topic of the
primary research. Including further clarification of an experimental protocol after addition of further
controls, or statistical reassessment of raw data.
Preliminary Findings Presentation of results from pilot studies which may establish a solid basis for
further investigations. Format similar to original research report but with more emphasis in discussion
of future studies and hypotheses arising from pilot study.

106

Commentaries Include articles that do not fit into the above criteria as original research. Includes
commentary and essays especially in regards to history, philosophy, professional, educational, clinical,
ethical, political and legal aspects of osteopathic medicine.
Clinical Practice Authors are encouraged to submit papers in one of the following formats: Case
Report, Case Problem, and Evidence in Practice.
Case Reports usually document the management of one patient, with an emphasis on presentations that
are unusual, rare or where there was an unexpected response to treatment e.g. an unexpected side effect
or adverse reaction. Authors may also wish to present a case series where multiple occurrences of a
similar phenomenon are documented. Preference will be given to reports that are prospective in their
planning and utilise Single System Designs, including objective measures.
The aim of the Case Problem is to provide a more thorough discussion of the differential diagnosis of a
clinical problem. The emphasis is on the clinical reasoning and logic employed in the diagnostic
process.
The purpose of the Evidence in Practice report is to provide an account of the application of the
recognised Evidence Based Medicine process to a real clinical problem. The paper should be written
with reference to each of the following five steps: 1. Developing an answerable clinical question. 2.
The processes employed in searching the literature for evidence. 3. The appraisal of evidence for
usefulness and applicability. 4. Integrating the critical appraisal with existing clinical expertise and
with the patient's unique biology, values, and circumstances. 5. Reflect on the process (steps 1-4),
evaluating effectiveness, and identifying deficiencies.
Presentation of Typescripts
Your article should be typed on A4 paper, double-spaced with margins of at least 3cm. Number all
pages consecutively beginning with the title page.
To facilitate anonymity, the author's names and any reference to their addresses should only appear on
the title page. Please check your typescript carefully before you send it off, both for correct content and
typographic errors. It is not possible to change the content of accepted typescripts during production.
Papers should be set out as follows, with each section beginning on a separate page:
Title page
To facilitate the peer-review process, two title pages are required. The first should carry just the title of
the paper and no information that might identify the author or institution. The second should contain
the following information: title of paper; full name(s) and address(es) of author(s) clearly indicating
who is the corresponding author; you should give a maximum of four degrees/qualifications for each
author and the current relevant appointment only; institutional affiliation; name, address, telephone, fax
and e-mail of the corresponding author; source(s) of support in the form of funding and/or equipment.
Keywords
Include three to ten keywords. These should be indexing terms that may be published with the abstract
with the aim of increasing the likely accessibility of your paper to potential readers searching the
literature. Therefore, ensure keywords are descriptive of the study. Refer to
http://www.nlm.nih.gov/mesh/meshhome.html for the MeSH thesaurus.
Abstract
Both qualitative and quantitative research approaches should be accompanied by a structured abstract.
Commentaries and Essays may continue to use text based abstracts of no more than 150 words. All
original articles should include the following headings in the abstract as appropriate: Background,
Objective, Design, Setting, Methods, Subjects, Results, and Conclusions. As an absolute minimum:
Objectives, Methods, Results, and Conclusions must be provided for all original articles. Abstracts for
reviews of the literature (in particular systematic reviews and meta-analysis) should include the
following headings as appropriate: Objectives, Data Sources, Study Selection, Data Extraction, Data
Synthesis, Conclusions. Abstracts for Case Studies should include the following headings as
appropriate: Background, Objectives, Clinical Features, Intervention and Outcomes, Conclusions.

107

Text
The text of observational and experimental articles is usually, but not necessarily, divided into sections
with the headings; introduction, methods, results, results and discussion. In longer articles, headings
should be used only to enhance the readability. Three categories of headings should be used:
major ones should be typed in capital letter in the centre of the page and underlined
secondary ones should be typed in lower case (with an initial capital letter) in the left hand margin and
underlined
minor ones typed in lower case and italicised

Do not use 'he', 'his' etc. here the sex of the person is unknown; say 'the patient' etc. Avoid inelegant
alternatives such as 'he/she'. Avoid sexist language.
Statement of Competing Interests
When submitting a Research report you will need to consider if you, or any of your co-authors, are an
Editor or Editorial Board member of the International Journal of Osteopathic Medicine. If this is the
case you will need to include a section, at the end of your manuscript immediately before the reference
section, called "Statement of Competing Interests". Example statement, which may require editing, is
as follows: {Name of author} is an Editor of the Int J Osteopath Med; {Name of author} is a member
of the Editorial Board of the Int J Osteopath Med but was not involved in review or editorial decisions
regarding this manuscript.
References
Responsibility for the accuracy of bibliographic citations lies entirely with the Authors.
Citations in the text: Please ensure that every reference cited in the text is also present in the reference
list (and vice versa). Avoid using references in the abstract. Unpublished results and personal
communications are not recommended in the reference list, but may be mentioned in the text. If these
references are included in the reference list they should follow the standard reference style of the
journal and should include a substitution of the publication date with either "Unpublished results" or
"Personal communication" Citation of a reference as "in press" implies that the item has been accepted
for publication.
Text: Indicate references by superscript numbers in the text. The actual Authors can be referred to, but
the reference number(s) must always be given.
List: Number the references in the list in the order in which they appear in the text.
Examples:
Reference to a journal publication:
1. Van der Geer J, Hanraads JAJ, Lupton RA. The art of writing a scientific article. J Sci Commun
2000;163:51-9.
Reference to a book:
2. Strunk Jr W, White EB. The elements of style. 3rd ed. New York: Macmillan; 1979.
Reference to a chapter in an edited book:
3. Mettam GR, Adams LB. How to prepare an electronic version of your article. In: Jones BS, Smith
RZ, editors. Introduction to the electronic age. New York: E-Publishing Inc; 1999, p. 281-304
Note shortened form for last page number. e.g., 51-9, and that for more than 6 Authors the first 6
should be listed followed by "et al." For further details you are referred to "Uniform Requirements for
Manuscripts submitted to Biomedical Journals" (J Am Med Assoc 1997;277:927-934) (see also
http://www.nejm.org/general/text/requirements/1.htm)

108

Citing and listing of Web references. As a minimum, the full URL should be given. Any further
information, if known (Author names, dates, reference to a source publication, etc.), should also be
given. Web references can be listed separately (e.g., after the reference list) under a different heading if
desired, or can be included in the reference list.
Tables, Illustrations and Figures
A detailed guide on electronic artwork is available on our website: http://www.elsevier.com/authors
Preparation of supplementary data. Elsevier now accepts electronic supplementary material (ecomponents) to support and enhance your scientific research. Supplementary files offer the Author
additional possibilities to publish supporting applications, movies, animation sequences, highresolution images, background datasets, sound clips and more. Supplementary files supplied will be
published online alongside the electronic version of your article in Elsevier Web products, including
ScienceDirect: http://www.sciencedirect.com. In order to ensure that your submitted material is
directly usable, please ensure that data is provided in one of our recommended file formats. Authors
should submit the material in electronic format together with the article and supply a concise and
descriptive caption for each file. For more detailed instructions please visit our artwork instruction
pages at http://www.elsevier.com/authors.
Illustrations and tables that have appeared elsewhere must be accompanied by written permission
to reproduce them from the original publishers. This is necessary even if you are an author of the
borrowed material. Borrowed material should be acknowledged in the captions in the exact wording
required by the copyright holder. If not specified, use this style: `Reproduced by kind permission of . . .
(publishers) from . . . (reference).' Identifiable clinical photographs must be accompanied by
written permission from the patient.
The text of original research for a quantitative or qualitative study is typically subdivided into the
following sections:
Introduction
State the purpose of the article. Summarise the rationale for the study or observation. Give only strictly
pertinent references and do not review the subject extensively. Do not include data or conclusions from
the work being reported.
Materials and Methods
Describe your selection of observational or experimental subjects (including controls). Identify the
methods, apparatus (manufacturer's name and address in parenthesis) and procedures in sufficient detail
to allow workers to reproduce the results. Give references and brief descriptions for methods that have
been published but are not well known; describe new methods and evaluate limitations.
Indicate whether procedures followed were in accordance with the ethical standards of the institution or
regional committee responsible for ethical standards. Do not use patient names or initials. Take care to
mask the identity of any subjects in illustrative material.
Results
Present results in logical sequence in the text, tables and illustrations. Do not repeat in the text all the
data in the tables or illustrations. Emphasise or summarise only important observations.
Discussion
Emphasise the new and important aspects of the study and the conclusions that follow from them. Do
not repeat in detail data or other material given in the introduction or the results section. Include
implications of the findings and their limitations, include implications for future research. Relate the
observations to other relevant studies. Link the conclusion with the goals of the study, but avoid
unqualified statements and conclusions not completely supported by your data. State new hypothesis
when warranted, but clearly label them as such. Recommendations, when appropriate, may be
included.

109

Acknowledgments
In the appendix one or more statements should specify (a) contributions that need acknowledging, but
do not justify authorship (b) acknowledgments of technical support (c) acknowledgments of financial
and material support, specifying the nature of the support. Persons named in this section must have
given their permission to be named. Authors are responsible for obtaining written permission from
those acknowledged by name since readers may infer their endorsement of the data and conclusions.
IJOM Author Contribution Statement
All manuscripts submitted to the journal should be accompanied by an Author Contribution Statement.
The purpose of the Statement is to give appropriate credit to each author for their role in the study. All
persons listed as authors should have made substantive intellectual contributions to the research. To
qualify for authorship each person listed should have made contributions in each of the following;
1) Contributions to conception and design; data acquisition; data analysis and interpretation;
2) Drafting of manuscript, or critical revision for important intellectual content;
3) All authors must have given approval to the final version of the manuscript submitted for
consideration to publish.
Acquisition of funding; provision of resources; data collection; or general supervision, alone, is not
sufficient justification for authorship. Contributors who do not meet the criteria for authorship as
outlined above should be listed in the Acknowledgements section. Acknowledgements may include
contributions of technical assistance, proof reading and editing, or assistance with resources and
funding. The statement may be published in the paper as appropriate.
Example of suggested format. Note the use of author initials.
AB conceived the idea for the study. AB and CD contributed to the design and planning of the
research. All authors were involved in data collection. AB and EF analysed the data. AB and CD wrote
the first draft of the manuscript. EF coordinated funding for the project. All authors edited and
approved the final version of the manuscript.
Funding body agreements and policies
Elsevier has established agreements and developed policies to allow authors whose articles appear in
journals published by Elsevier, to comply with potential manuscript archiving requirements as
specified as conditions of their grant awards. To learn more about existing agreements and policies
please visit http://www.elsevier.com/fundingbodies
Copyright
Upon acceptance of an article, authors will be asked to sign a "Journal Publishing Agreement'" (for
more information on this and copyright see http://www.elsevier.com/copyright. Acceptance of the
agreement will ensure the widest possible dissemination of information. An e-mail (or letter) will be
sent to the corresponding author confirming receipt of the manuscript together with a 'Journal
Publishing Agreement' form or a link to the online version of this agreement. If excerpts from other
copyrighted works are included, the author(s) must obtain written permission from the copyright
owners and credit the source(s) in the article. Elsevier has preprinted forms for use by authors in these
cases: contact Elsevier's Rights Department, Philadelphia, PA, USA: phone (+1) 215 239 3804, fax
(+1) 215 239 3805, healthpermissions@elsevier.com . Requests may also be completed online via the
Elsevier homepage http://www.elsevier.com/locate/permissions.
Page Proofs
One set of page proofs will be sent by e-mail to the corresponding author (if we do not have an e-mail
address then paper proofs will be sent by post). Elsevier now sends PDF proofs which can be
annotated, for this you will need to download Adobe Reader version 7 (or higher) available free from
http://www.adobe.com/products/acrobat/readstep2.html. Instructions on how to annotate PDF files will
accompany the proofs. The exact system requirements are given at the Adobe site:
http://www.adobe.com/products/acrobat/acrrsystemreqs.html#70win.
If you do not wish to use the PDF annotations function, you may list the corrections (including replies
to the Query Form) and return to Elsevier in an e-mail. Please list your corrections quoting line
number. If, for any reason, this is not possible, then mark the corrections and any other comments
(including replies to the Query Form) on a printout of your proof and return by fax, or scan the pages
and e-mail, or by post.

110

Please use this proof only for checking the typesetting, editing, completeness and correctness of the
text, tables and figures. Significant changes to the article as accepted for publication will only be
considered at this stage with permission from the Editor. We will do everything possible to get your
article published quickly and accurately. Therefore, is it important to ensure that all of your corrections
are sent back to us in one communication, please check carefully before replying, as inclusion of any
subsequent corrections cannot be guaranteed. Proofreading is solely your responsibility. Note that
Elsevier may proceed with the publication of your article if no response is received.
Author Enquiries
For enquiries relating to the submission of articles (including electronic submission where available)
please visit this journal s homepage at http://www.elsevier.com/locate/ijosm. You can track accepted
articles at http://www.elsevier.com/trackarticle and set up e-mail alerts to inform you of when an
article s status has changed. Also accessible from here is information on copyright, frequently asked
questions and more.
Contact details for questions arising after acceptance of an article, especially those relating to proofs,
will be provided by the publisher.
Language services. Authors who require information about language editing and copyediting services
pre- and post-submission please visit
http://www.elsevier.com/wps/find/authorshome.authorslocate/languagepolishing or contact
authorsupport@elsevier.com for more information. Please note Elsevier neither endorses nor takes
responsibility for any products, goods or services offered by outside vendors through our services or in
any advertising. For more information please refer to our Terms and Conditions
http://www.elsevier.com/termsandconditions.
Offprints
The corresponding author, at no cost, will be provided with a PDF file of the article via e-mail or,
alternatively, 25 free paper offprints. The PDF file is a watermarked version of the published article
and includes a cover sheet with the journal cover image and a disclaimer outlining the terms and
conditions of use. Additional paper offprints can be ordered by the authors. An order form with prices
will be sent to the corresponding author.
Checklist
Please check your typescript carefully before you send it off to the Editorial Office, both for correct
content and typographical errors, as it is not possible to change the content of accepted typescripts
during the production process.
One copy of typescript and illustrations
Reference list in correct style
Written Permission from original publishers and authors to reproduce any borrowed any borrowed
material

111