Accepted Manuscript

Blood Flow Restriction induces hypoalgaesia in recreationally active adult male

anterior knee pain patients allowing therapeutic exercise loading

Korakakis Vasileios, Whiteley Rodney, Epameinontidis Konstantinos

PII: S1466-853X(17)30503-5
DOI: 10.1016/j.ptsp.2018.05.021
Reference: YPTSP 912

To appear in: Physical Therapy in Sport

Received Date: 24 September 2017

Revised Date: 24 March 2018
Accepted Date: 29 May 2018

Please cite this article as: Vasileios, K., Rodney, W., Konstantinos, E., Blood Flow Restriction induces
hypoalgaesia in recreationally active adult male anterior knee pain patients allowing therapeutic exercise
loading, Physical Therapy in Sports (2018), doi: 10.1016/j.ptsp.2018.05.021.

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TILTE PAGE

Title: Blood Flow Restriction induces hypoalgaesia in anterior knee pain patients

allowing therapeutic exercise loading.

Authors:

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Korakakis Vasileios, PT, PhD1,2 Whiteley Rodney, PT, PhD1 and Epameinontidis

Konstantinos, PT1

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Aspetar, Orthopaedic and Sports Medicine Hospital, Doha, Qatar
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Hellenic Orthopaedic Manipulative Therapy Diploma (HOMTD), Athens, Greece

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Corresponding author: Korakakis Vasileios
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Aspetar, Orthopaedic and Sports Medicine Hospital, Doha, Qatar

Doha, PO Box29222, Qatar

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Tel: +97466672809, Email: Vasileios.Korakakis@aspetar.com

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or vkorakakis@hotmail.com
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Conflicts of interest and source of funding: None declared

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Ethics approval: Granted from Anti-Doping Lab Qatar (ADLQ – ethics board)
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Acknowledgements The authors would like to thank the following physiotherapist

for their contribution in the study: Azzopardi Matthew, Cole Andrew, Itani Abdallah,

and Nunnes Pedro.

Contributors KV, WR and EK contributed to the conception and design of the study.

KV performed BFR assessment and protocol, extracted and analysed the data, and
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wrote the manuscript. WR and EK critically revised and edited the manuscript for

intellectual content.

Word count: 2872

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Title: “Blood Flow Restriction induces hypoalgaesia in recreationally

active adult male anterior knee pain patients allowing therapeutic
exercise loading”

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Abstract

Objective: To evaluate if a single blood flow restriction (BFR)-exercise bout would

induce hypoalgaesia in patients with anterior knee pain (AKP) and allow painless

application of therapeutic exercise.

Design: Cross-sectional repeated measures design.

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Setting: Institutional out-patients physiotherapy clinic.

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Patients: Convenience sample of 30 AKP patients.

Intervention: BFR was applied at 80% of complete vascular occlusion. Four sets of

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low-load open kinetic chain knee extensions were implemented using a pain

monitoring model.

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Main Outcome Measurements: Pain (0-10) was assessed immediately after BFR
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application and after a physiotherapy session (45 minutes) during shallow and deep
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single-leg squat (SSLS, DSLS), and step-down test (SDT). To estimate the patient

rating of clinical effectiveness, previously described thresholds for pain change

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(≥40%) were used, with appropriate adjustments for baseline pain levels.
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Results: Significant effects were found with greater pain relief immediate after BFR

in SSLS (d=0.61, p<0.001), DSLS (d=0.61, p<0.001), and SDT (d=0.60, p<0.001).
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Time analysis revealed that pain reduction was sustained after the physiotherapy
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session for all tests (d(SSLS)=0.60, d(DSLS)=0.60, d(SDT)=0.58, all p<0.001). The
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reduction in pain effect size was found to be clinically significant in both post-BFR

assessments.

Conclusion: A single BFR-exercise bout immediately reduced AKP with the effect

sustained for at least 45 minutes.

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Keywords: Blood flow restriction, Occlusion, Resistance training, Ischaemia,

Rehabilitation

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INTRODUCTION

Anterior knee pain (AKP) is an umbrella term describing a variety of symptomatic

clinical presentations including: patellofemoral pain, patellar tendinopathy, fat pad or

plica impingement.(Malliaras, Cook, Purdam, & Rio, 2015; Post & Fulkerson, 1994;

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Wood, Muller, & Peat, 2011) Key aspects of the clinical presentation of AKP are

quadriceps wasting, altered muscle function, and diffuse pain over the anterior

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aspect of the knee that is aggravated by knee joint-loading.(Crossley et al., 2007; H.

F. Hart, Ackland, Pandy, & Crossley, 2012; Malliaras et al., 2015; Suter, Herzog, &

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Bray, 1998; Witvrouw et al., 2014)

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The effect of exercise in musculoskeletal conditions, including AKP, may be
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attenuated in the presence of pain, (Chiu, Wong, Yung, & Ng, 2012; Giles, Webster,

McClelland, & Cook, 2017; Herrington & Al-Sherhi, 2007) mainly because pain has a
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detrimental effect in muscle function and motor control.(Aminaka, Pietrosimone,

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Armstrong, Meszaros, & Gribble, 2011; J. M. Hart, Pietrosimone, Hertel, & Ingersoll,
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2010; Henriksen, Rosager, Aaboe, Graven-Nielsen, & Bliddal, 2011) Evidence

suggests that pain is associated with an adaptation in motor behaviour involving

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redistribution of activity within and between muscles, changes in mechanical

behaviour, and changes at multiple levels of the motor system.(Hodges, 2011).

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Experimental knee pain studies (Henriksen et al., 2011; Hodges, Mellor, Crossley, &
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Bennell, 2009; Park & Hopkins, 2013) have demonstrated that AKP leads to

immediate decrease in quadriceps and hamstrings peak torque and changes in

motor control. A significant association has also been reported between pain

intensity and change in muscle strength and performance in both experimental and

clinical AKP (Henriksen et al., 2011; Yosmaoglu et al., 2013). A number of clinical

interventions target changes in motor control that accompany pain.(Espí-López,

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Arnal-Gómez, Balasch-Bernat, & Inglés, 2017; Riel et al., 2018; E. Rio et al., 2016)

These interventions use relearning strategies in order to alter adapted motor features

that are considered to contribute to the presence of pain.(Hodges, 2011)

Nevertheless, it has been suggested that pain may affect learning processes or

painful exercises may affect motor control due to modified performance of the task

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during pain.(Boudreau et al., 2007) Given the former, exercise-induced analgesia

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would have an essential clinical impact. Recent research suggests isometric

exercise induces analgesia in anterior knee pain albeit in a small sample limited to

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patellar tendinopathy.(Ebonie Rio et al., 2015) Additionally, low load quadriceps

strengthening with blood flow restriction (BFR) produced greater reduction in pain

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with daily living at short-term follow-up in patients with patellofemoral pain.(Giles et
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al., 2017)
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BFR training involves application of a constricting inflatable cuff to the limb, with aim

to maintain arterial inflow, while occluding venous return during exercise.(Loenneke,

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Wilson, Marin, Zourdos, & Bemben, 2012) Evidence suggests that low-load
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resistance training with BFR can induce muscle hypertrophy and improve strength in
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healthy individuals,(Scott, Loenneke, Slattery, & Dascombe, 2016; Slysz, Stultz, &

Burr, 2016) in patients with patellofemoral pain,(Giles et al., 2017) in the

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elderly,(Yasuda et al., 2014) in patients after anterior cruciate ligament

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reconstruction,(Ohta et al., 2003),in patients after knee arthroscopy,(Tennent et al.,

2016) in women with risk factors for knee osteoarthritis,(Segal, Williams, Davis,

Wallace, & Mikesky, 2015) and can attenuate disuse atrophy during periods of

immobilisation.(Kubota, Sakuraba, Sawaki, Sumide, & Tamura, 2008) However,

limited number of studies involving BFR training has been conducted in clinical

populations. Anecdotally we noticed immediate reduction in pain after application of

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BFR in patients with AKP. To our knowledge this effect has not been examined

formally.

The primary objective of the present study was to evaluate if a single acute BFR low-

load-exercise bout would induce meaningful pain reduction in patients with AKP.

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METHODS

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Subjects

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In this repeated measures single-blinded pilot study a single cohort (convenience

sample) of 30 male patients suffering from AKP participated (Table 1).

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Recruitment followed a sample size calculation accounted for a type-I error rate of
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0.05, and a power of 80%. The assumptions of a delta of 3.0 points in pain rating on

the numeric rating scale (SD=2.0) were based on data of a study assessing the
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significant pain change from the patient’s perspective.(Farrar, Young Jr, LaMoreaux,
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Werth, & Poole, 2001)

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Ethics approval and written informed consent were sought and obtained.
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Inclusion in the study, initial evaluation and baseline testing

We enrolled adult patients who had consulted a sports medicine physician in a

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primary-care setting for AKP complaints. This study has been designed (Figure 1)
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and reported in line with the recommendations for intervention description and

replication guide (TIDieR)(Hoffmann et al., 2014) (Online supplemental file).

A standardised history and physical examination was conducted by a physiotherapist

on each patient. If the patient met the inclusion criteria, he was re-evaluated by a

second senior physiotherapist who conducted the baseline testing and applied the

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BFR protocol. Baseline testing involved three clinical tests (shallow single leg squat,

deep single leg squat, and 20cm step down) and the patients were asked to rate

their pain on an 11-point numeric rating scale (NRS) (0-10). The standardised clinical

tests are described in Figure 2.

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Blood flow restriction pressure calculation

BFR devices partially restrict arterial while occluding venous blood flow, and cause

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pooling of blood in capacitance vessels distal to the cuff. (Loenneke, Wilson, Wilson,

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Pujol, & Bemben, 2011) To attain a personalised partial vascular occlusion for use in

clinical practise a standardized procedure ("Recommended practices for the use of

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the pneumatic tourniquet in the perioperative practice setting," 2007) was followed by
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an experienced physiotherapist. All the participants were asked to lie in prone

position and rest for 5 minutes. A wide (Loenneke, Fahs, et al., 2012) BFR cuff
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(Sports Rehab Tourniquet©) of 10 cm width and 116 cm length was attached to the
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participants’ proximal thigh at the inguinal fold region. A vascular Doppler probe was
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placed over the popliteal artery in order to capture its auscultatory pulse. To

determine the pressure (in mmHg) necessary for complete vascular occlusion the
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cuff was then inflated to the point at which the pulse was eliminated, and this

pressure was recorded. Based on previous clinical and strength training

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research(Lixandrao et al., 2015; Tennent et al., 2017) partial vascular occlusion was
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set at 80% of that pressure, and Doppler confirmation of partial arterial flow was

established.

Blood flow restriction intervention protocol

Patients were familiarised with the exercise intervention with the BFR device in place

(not inflated). The low-load resistance training consisted of open kinetic chain knee

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extensions (90º-0º) performed slowly (2 seconds concentric, 2 seconds eccentric

phase, paced by a metronome).(Ebonie Rio et al., 2015) A modified pain monitoring

approach(Silbernagel, Thomee, Eriksson, & Karlsson, 2007; Silbernagel, Thomee,

Thomee, & Karlsson, 2001; Thomee, 1997) dictated the loading to a maximum of

5kg (variable ankle weights) such that the patient reported a maximum of 4/10 during

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familiarisation (without BFR inflation). Patients were then instructed to perform four

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sets of knee extensions; one set to maximum possible repetitions, then three sets of

15 repetitions with 30 seconds rest between sets. Termination of the first set was

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indicated either by inability to follow the pace of the metronome or inability to fully

extend the knee joint. The BFR-cuff was kept inflated throughout the session.

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Attention was paid that all repetitions were performed at each set and in case that
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the patient was not able to finish the repetitions the weight was reduced accordingly.
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Post-BFR interventions
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Immediately after the BFR exercise session the same three functional tests were
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carried out (shallow single leg squat, deep single leg squat, and 20cm step down)

and the pain was rated (Figure 1).

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Subsequently, all participants underwent a standardised physical therapy session.

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Finally a third blinded assessor re-examined the functional tests and recorded pain
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levels.

Statistical analysis

Data were found to be non-normally distributed. Hence a Friedman’s ANOVA with

post-hoc Wilcoxon signed-rank tests for pairwise comparisons of medians for each

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dependent variable were applied when significant interactions were found. The level

of significance was set at 0.05, and the Bonferroni adjustment was set at 0.017.

A standardised effect size of pain reduction was calculated following the formula

Z/√N, where Z was the value obtained from the Wilcoxon signed-rank tests and N

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the number of observations over the two time points (N=60, casesX2). Clinical

interpretation of the effect sizes was based on Cohen’s cut-points:(Cohen, 1988)

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effect sizes greater than 0.8 were considered large, from 0.8 to 0.5 moderate, and

those less than 0.5 small.

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We aimed also to evaluate the effect of pain reduction in patient rated terms. The

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patient’s experience of change in pain (“improvement” or “worsening”) is seen to vary
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according to their baseline levels of pain such that a reduction of 1 point on a NRS is

perceived differently if your baseline level is 9 or 3, for example. Two approaches are
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documented attempting to overcome these limitations. Some researchers advocate

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using a percentage reduction as denoting clinically meaningful change in pain as for

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example Ostelo et al.(Ostelo et al., 2008) Alternately, Farrar et al(Farrar et al., 2001)

examined both the NRS pain change and the individual patient’s rating of the change
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in pain on a 7-point Likert scale ranging from “very much improved” to “very much

worsened.” They showed that the patient rating was not distributed equally across
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the categorisations when adjusting for the baseline level of pain. Accordingly,
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clinically meaningful change in pain was set as a pain reduction greater than 40%

from baseline.(Farrar et al., 2001)

RESULTS

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The median and interquartile range (IQR) of the pain scores obtained from testing

procedures at each time measurement are presented in Table 2 and depicted in

Figure 3.

The Friedman test, which evaluated differences in medians among the three test

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occasions, was significant for the three functional tests examined. For single-leg

squat (shallow) pain score x2(2, N=30)=46.208, p<0.001 with a Kendall’s coefficient

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of concordance of 0.77 indicating strong differences, for single-leg squat (deep) pain

score x2(2, N=30)=44.855, p<0.001 with Kendall’s W of 0.748 indicating strong

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differences, and for step-down pain score x2(2, N=30)=41.152, p<0.001 with a

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Kendall’s W of 0.686 indicating moderate differences.
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Pair-wise comparisons using Wilcoxon test showed significant differences in pain

scores from baseline to the 2 follow-up scores in all clinical tests with moderate (all
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>0.58) effect sizes (Table 3). Individual data (N=30) are presented in Appendix.
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The percentage reduction of median pain scores for single-leg squat (shallow) and
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step-down test at both post-BFR and post-PT session evaluations were 60%. The

magnitude of this reduction indicated a clinically meaningful change in pain from

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patient’s experience and can be rated as ‘very much improved’.(Farrar et al., 2001)
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The percentage reduction of median pain scores for single-leg squat (deep) at post-
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BFR was 64.3% and at post-PT session was 57.1%. The magnitude of this reduction

indicated a clinically meaningful change in pain from patient’s experience and can be

rated as ‘very much improved’ at both occasions.(Farrar et al., 2001)

DISCUSSION

BFR with low load exercise reduces pain

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A single low-load BFR exercise bout reduced AKP immediately and the effect

sustained for at least 45 minutes. The effect sizes for pain reduction in all procedures

were moderate to large which were clinically significant as estimated in patient-rated

terms. Importantly the reduction in pain allowed the patients to perform exercises

with knee loading, which were typically otherwise associated with symptoms. We

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note that no patients reported any adverse effects or symptom exacerbation during

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this trial.

BFR and exercise independently induce hypoalgaesia

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In the present study low-load BFR exercise led to decreased pain perception in

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loaded lower limb functional testing and training for at least 45 minutes. Evidence
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suggests that acute exercise reduces sensitivity to painful stimuli in healthy

individuals and chronic pain populations, but there is limited evidence for painful
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musculoskeletal conditions(Naugle, Fillingim, & Riley, 2012; Ebonie Rio et al., 2015)
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- a phenomenon termed exercise-induced hypoalgaesia.(Koltyn, 2002) Large effect

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sizes have been reported for reduced pain perception of experimentally induced pain

following isometric or dynamic resistance exercise.(Naugle et al., 2012) From a

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clinical perspective, the duration of this hypoalgaesic effect plays an important role

for the use of isometric or resistance exercise as a method to enhance rehabilitation

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of clinical pain symptoms such as AKP. The data from experimentally induced pain
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suggests that the isometric or dynamic resistance exercise induced hypoalgaesia

attenuates over time, with the window of effectiveness ranging between 10 and 30

minutes.(Naugle et al., 2012) To our knowledge, this study implementing slow low-

load BFR resistance training in AKP and another study(Ebonie Rio et al., 2015)

implementing isometric exercises for patellar tendinopathy are the only reports in the

literature regarding lower limb musculoskeletal conditions showing an acute

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exercise-induced hypoalgaesic effect lasting at least 45 minutes post exercise. The

clinical implications are that low-load BFR exercise may be used to reduce pain and

provide a window of opportunity for clinicians to optimally load otherwise painful

tissues and joints.

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BFR and low load exercise allow higher intensity training that would otherwise

be painful

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Muscle strengthening can reduce pain and improve function in AKP patients

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following treatment programs for at least 4-6 weeks.(Crossley et al., 2016; Kooiker,

Van De Port, Weir, & Moen, 2014; Lack, Barton, Sohan, Crossley, & Morrissey,

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2015) However, aggravation of symptoms forces clinicians to reduce resistance load,
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likely resulting in attenuation of strength improvement and muscle hypertrophy.(Chiu

et al., 2012; Giles et al., 2017; Herrington & Al-Sherhi, 2007) Meaningful
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improvements in hypertrophy and strength have been documented using low-load

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(20-30% of 1RM) BFR training, although it should be noted that these gains are not
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as great as traditional high load training.(Hughes, Paton, Rosenblatt, Gissane, &

Patterson, 2017; Slysz et al., 2016)

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We suggest that two broad strategies could be implemented clinically in AKP: i)

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modification of optimal tissue loading to a level that does not provoke symptoms; or
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ii) reduction of pain preceding the normal tissue loading session by BFR induced

hypoalgaesia.

Recent research(Giles et al., 2017) in patellofemoral pain patients assessed the

effectiveness of low-load BFR strengthening (30% of 1RM, 1 set of 30 repetitions

and 3 sets of 15 repetitions) compared to usual strengthening (approximately 70% of

1RM, 3 sets of 7-10 repetitions) using a pain monitoring model. This study showed

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no significant between groups change in quadriceps muscle thickness, worst pain,

pain with activities of daily living and Kujala Patellofemoral Score at 6-month follow-

up. This research suggests that the lower load training associated with BFR had

comparable effectiveness despite the reduced absolute load with BFR training. We

note that the clinical significance of this approach needs to be considered in light of

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the changes in quadriceps muscle thickness. The increase from baseline of 4.0%

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and 1.1% of quadriceps thickness for standardised strengthening and BFR group

respectively is far less than the expected increase of at least 7% in healthy

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individuals.(Abe, DeHoyos, Pollock, & Garzarella, 2000) This significant difference

could be attributed to submaximal strength gains due to reduced absolute load as a

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result of pain and/or a reduced range of motion employed during the training (0°-60º
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leg press and 90°-45º leg extension).(Giles et al., 2017) Potentially the pain
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reduction documented in the present study could allow for higher absolute training

loads and thus greater strength gains in these patients.

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Mechanisms of action for BFR-induced hypoalgaesia are unclear

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Presently, although the effect of BFR-induced hypoalgaesia appears to be a robust

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finding, the mechanisms remain unclear. Suggestions include: conditioned pain

modulation,(Fujii, Motohashi, & Umino, 2006; Hollander et al., 2010; Oono, Nie,
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Matos, Wang, & Arendt-Nielsen, 2011; Pud, Granovsky, & Yarnitsky, 2009; Pud,
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Sprecher, & Yarnitsky, 2005; Tuveson, Leffler, & Hansson, 2006) exercise related

release of endogenous substances which inhibit nociceptive pathways,(de Souza,

Duarte, & de Castro Perez, 2013; Dietrich & McDaniel, 2004; Galdino, Duarte, &

Perez, 2010; Galdino et al., 2015; Koltyn, Brellenthin, Cook, Sehgal, & Hillard, 2014;

Zouhal, Jacob, Delamarche, & Gratas-Delamarche, 2008) and induced hypoxia

following BFR training.(Faiss et al., 2013; Galdino et al., 2015; Luo & Cizkova, 2000)

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The diffuse noxious inhibitory controls (DNIC)-like effect or heterotopic noxious

conditioning stimulation or “pain inhibits pain” effect is a “bottom-up” activation of the

pain-modulation mechanism, as part of the descending endogenous analgesia

system. An ascending noxious input from a remote body area (conditioning stimulus)

exerts descending analgesia on the perception of another noxious stimulus.(Pud et

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al., 2009) Experimental studies in healthy individuals have shown significant

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decrease in pain intensities after a noxious “conditioning” stimulus at adjacent and

remote sites when stimulated.(Oono et al., 2011; Pud et al., 2009; Pud et al., 2005)

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Conditioning stimulation by using an ischemic pain model has been shown to

produce a DNIC after-effect that lasted from 5 up to 30 minutes following cuff

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deflation.(Fujii et al., 2006; Tuveson et al., 2006) In the present study the
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conditioning stimulus may be originated from the combination of ischemic and
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exercise-induced muscle pain and/or the cuff pressure itself. Muscle pain occurs

naturally during resistance exercise,(Cook, O'Connor, Eubanks, Smith, & Lee, 1997)
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however when BFR with low-load is applied during dynamic resistance exercise,
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both pain and effort sense are altered to a similar degree as exercise using greater

load without BFR.(Hollander et al., 2010) It has been hypothesised (Hollander et al.,
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2010) that hypoxia and decreased metabolite clearance coupled with arterial
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mechanical deformation and significantly reduced arterial circulation could create

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and enhanced perception of pain. Additionally, cuff inflation at higher pressures, as

used in the current study (80% of complete occlusion) has been previously

characterised as moderately painful(Jones, Taylor, & Barry, 2017). Accordingly, the

addition of exercise with BFR would likely be sufficient to induce pain and therefore a

CPM effect.

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Exercise-induced or hypoxia-induced production of substances that influence

nociceptor sensitivity cannot be excluded as a mechanism of action in low-load BFR-

induced hypoalgesia. Substances like opioids, cannabinoids, cateholamines and

nitric oxide have been shown to contribute in exercise-induced analgesia in both

animal and human studies(de Souza et al., 2013; Dietrich & McDaniel, 2004; Galdino

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et al., 2010; Galdino et al., 2015; Koltyn et al., 2014; Zouhal et al., 2008) through

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different pathways and mechanisms that may be reinforced by BFR. Also, research

indicates that hypoxic conditions, similar to the anaerobic environment created by

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BFR exercise, affected concentration of biochemical mediators like nitric oxide,(Faiss

et al., 2013) that seem to have beneficial effects for the inhibition of nociceptive

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pathways in animal and human studies.(Galdino et al., 2015; Luo & Cizkova, 2000)
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The decrease in pain post BFR training in the present study may be attributed to the
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effect of: arterial occlusion, or slow low-load exercise, or the combination of both.

Preliminary evidence(Bryk et al., 2016; Giles et al., 2017; Segal et al., 2015)
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demonstrates alleviation of condition-related pain following BFR training. It is

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possible that low-load BFR training has a pain modulating effect as the BFR group of
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patellofemoral pain patients(Giles et al., 2017) had significantly greater pain

reduction in pain with daily activities than the strengthening group, but only during
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the 8-week period of treatment. The substantial differences in pain reduction

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between the study of Giles et al,(Giles et al., 2017) and our study can be attributed to

the differences in arterial occlusion pressures and/or absolute load magnitude.

Despite that 40% of complete arterial occlusion produced comparable increases in

muscle hypertrophy, endurance and strength after 8 weeks of training to 90%

occlusion,(Counts et al., 2016) this effect has not been formally evaluated in terms of

BFR-induced hypoalgaesia. The former is suggestive that different combinations of

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arterial occlusion percentage and low-load may have dissimilar responses in

muscular adaptations or pain perception.

Limitations and Future research

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The present study employed a heterogeneous group of patients, all of whom were

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recreationally active males. Different outcomes may be found for sub-groups of

pathologies, different activity levels, or females. The cross-sectional nature of the

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study did not include a control group, and we have not assessed follow-up beyond

the immediate period of the intervention.

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Future research should include a control sham intervention as the lack of a control

group in this study means that we cannot discount the possibility that the effects
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seen are the result of the placebo effect. Future research is suggested to establish

the duration of hypoalgaesia, and the influence of varying BFR parameters on this
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effect. Long-term effects of the addition of BFR to usual care should be assessed in
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controlled studies, as well as any benefits of tailoring to sub-groups of presenting

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pathology. Finally, the mechanisms of action need to be further explored. If the

mechanisms are central, not peripheral, for example, BFR might be successfully
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applied away from the injured limb. If the mechanisms are local tissue-related in
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origin, then the parameters (pressure, time, load volume) need to be explored to

allow optimisation of the intervention.

What are the findings?

• A single low-load BFR exercise bout reduced AKP immediately and the effect

sustained for at least 45 minutes.

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• The effect sizes for pain reduction in all procedures were moderate to large

which were clinically significant as estimated in patient-rated terms.

How might this impact on clinical practice in the future?

• Clinically pain can prevent exercising at intensities high enough to be

efficacious in anterior knee pain. A single application of low load exercise with

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BFR appears to be a safe method of inducing hypoalgaesia and thereby

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allowing greater exercise intensity to be performed therapeutically.

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Conflict of interest: None declared

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Ethical approval: The study was approved by the institutional ethics committee and
all subjects gave informed consent
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Funding: None declared
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Table 1 Baseline characteristics of the participants

Characteristics n=30

Age, median(IQR), y 29 (24-34)

Male 30 (100)

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Duration of symptoms, median(IQR)/mean±SD, m 3 (2-8)/6.2±6.7
Arterial occlusion pressure (mean±SD) 115.8±9.6
Anterior knee pain

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Post-operative ACL reconstruction surgery 9 (30)
Patellofemoral pain 6 (20)
Meniscal injury (repair or menisectomy) 6 (20)

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Osteochondral defects 5 (16.7)
Patellar tendinopathy 2 (6.7)
Other 2 (6.7)
Data are number of subjects (percentage) unless otherwise indicated. Arterial

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occlusion pressure is presented in mmHg and corresponds to 80% of complete arterial
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occlusion pressure.
Abbreviations: y, years; m, months; IQR, interquartile range; SD, standard deviation
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Table 2 Descriptive values of pain scores at baseline, immediately after BFR with low
load resistance training and following a physical therapy session in all three functional
tests used as outcome measures in the study
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Clinical test Pre-BFR Post-BFR Post-PT session

Single leg squat* 5 (3-6) 2 (0.375-3) 2 (1-3.25)
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Single leg squat** 7 (4-8) 2.5 (1-4) 3 (1.75-5)

Step-down test 5 (3-7) 2 (0.75-4) 2 (1-3)
Values are presented as median(IQR range)
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*Shallow – To the mid-point between greater trochanter and popliteal crease

**Deep - To the level of the popliteal crease
Abbreviations: BFR, blood flow restriction training; IQR, interquartile range; PT
session, physical therapy session
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TABLE 3 Pairwise comparisons of pain scores at baseline, immediately after BFR

with low load resistance training and following a physical therapy session and
respective effect sizes of functional tests used in the study
Pre-BFR Pre-BFR Post-BFR
compared to compared to compared to
Post-BFR Post PT session Post PT session
Z=4.722, p=0.000 Z=4.649, p=0.000 Z=0.607, p=0.544
Single leg squat*
d=0.61 d=0.60 N/A
Z=4.727, p=0.000 Z=4.646, p=0.000 Z=1.308, p=0.191
Single leg squat**
d=0.61 d=0.60 N/A
Step-down test Z=4.630, p=0.000 Z=4.483, p=0.000 Z=0.416, p=0.678

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d=0.60 d=0.58 N/A
*Shallow – To the mid-point between greater trochanter and popliteal crease
**Deep - To the level of the popliteal crease
Abbreviations: BFR, blood flow restriction training; PT session, physical therapy
session.

Figure 1 Flowchart depicting: the enrolment process, inclusion and exclusion

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criteria, screening for eligibility, and intervention protocol of the study.

Abbreviations: BFR: blood flow restriction training; PT session: physical therapy

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session.

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Figure 2 The standardised tests used in the study to assess anterior knee pain. a)

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Single-leg squat (shallow): the patient was standing near a treatment bed with the
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height of the bed adjusted to be the mid-point of his thigh (half way between the

greater trochanter and popliteal crease), b) Single-leg squat (deep): the patient was
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standing near a treatment bed and the height of the bed was adjusted to the popliteal
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crease. The patient was required to touch but not sit on the surface of the bed, and
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c) Step-down test: the patient stepped down from a 20cm high step using his injured

limb in a slow and controlled manner, touching the ground and returning to the
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starting position. Immediately after each test the patient was questioned as to the

level of pain (0-10).

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Note. The tests are demonstrated by a physiotherapist of our rehabilitation

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department.

Figure 3 Pain scores depicted by box plots (median, IQR, and range) for a) single-

leg squat (shallow), b) single-leg squat (deep), and c) step-down test.

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Inclusion criteria Patients referred for
Enrollment

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• Age >18 years physiotherapy with anterior
• Diagnosis of anterior knee pain confirmed knee pain complaints by
by history, physical examination ± imaging physician (n=35)
• Pain in at least 1/3 functional tests

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Exclusion criteria
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Screening for eligibility in the study

• Unable to consent
• History of deep venous thrombosis (n=1)
• History of endothelial dysfunction
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• Peripheral vascular disease (n=1)

Excluded (n=5)
• Diabetes (n=1)
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• Infection
• Spinal or referred pain
• Bilateral knee symptoms (n=2)
• Previous experience of BFR training
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Patients met the eligibility criteria and

participated in the study (n=30)
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Physiotherapist A Physiotherapist B Physiotherapist C Physiotherapist D

(blinded) (blinded) (blinded)
Baseline testing
BFR pressure Post-BFR PT session (core, Post-PT session
Intervention

calculation evaluation strengthening, evaluation

BFR protocol stretching, balance)

Time in minutes
0 45
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What are the findings?

• A single low-load BFR exercise bout reduced AKP immediately and the effect

sustained for at least 45 minutes.

• The effect sizes for pain reduction in all procedures were moderate to large

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which were clinically significant as estimated in patient-rated terms.

How might this impact on clinical practice in the future?

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• Clinically pain can prevent exercising at intensities high enough to be

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efficacious in anterior knee pain. A single application of low load exercise with

BFR appears to be a safe method of inducing hypoalgaesia and thereby

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allowing greater exercise intensity to be performed therapeutically.
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