CONTENTS

1. INTRODUCTION.
2. DEFINITIONS OF PAIN.
3. HISTORICAL NOTE.
4. THE EVOLUTION OF PAIN.
5. CHANGING CONCEPTS OF PAIN.
6. PAIN RECEPTORS.
7. NEUROCHEMISTRY OF NOCICEPTIVIE PAIN.
8. THEORIES OF PAIN.
9. FACTORS AFFECTING PAIN.
10. NEURAL PATHWAYS OF PAIN.
- Neospinothalamic tract.
- Paleospinothalamic tract.
11. MODULATION OF PAIN.
- Gate Control Theory.
- Endogenous Pain Relief System.
- Gate Control Theory Revisited.
- Referred pain.
- Secondary hyperalgesia.
- Projected pain & phantom pain.
12.CONCLUSION.
 PAIN PATHWAYS

INTRODUCTION :
Pain is a sensory experience of special significance to physicians and
basic scientists. Pain is the commonest symptom which physicians are
called upon to treat. Apart from its obvious applied value, study of the
physiology of pain has taught us a lot about neural function in general. Pain
is an intensely subjective experience, and is therefore difficult to describe.
Bu tit has two features which are nearly universal. First, it is an unpleasant
experience; and secondly, it is evoked by a stimulus which is actually or
potentially damaging to living tissues. That is why, although it is
unpleasant, pain serves a protective function by making us aware of actual
or impending damage to the body. Like all sensory experiences, pain has
two components, the first component it the awareness of a painful stimulus
and the second is the emotional impact (or effect) evoked by the experience.
While the awareness is localized to the area stimulated, the experience
involves the whole being. That is why even when only a finger is hurt, the
whole person suffers. The two components of pain also imply that the same
painful experience may evoke widely different degrees of suffering in
different persons, and even in the same person under different
circumstances.
From a physiological point of view, there are two types of pain. One,
‘fast pain’, is conducted by faster conducting myelinated fibers, is well
localized, and is sharp or pricking in character. The other, ‘slow pain’ is
conducted by slower – conducting unmyelinated fibers, is poorly localized,
and is burning or dull and aching in character.
DEFINITIONS OF PAIN :
- International association for the study of pain (IASP) (WHO)
An unpleasant emotional experience associate with actual or
potential tissue damage or describe in terms of such damage.
-Bell
The subject’s conscious perception of modulated nociceptive
impulses that generate an unpleasant sensory and emotional
experiences associated with actual of potential tissue damage or
describe in terms of such damage.
- Monheim
An un pleasant emotional experience usually initiated by noxious
stimulus and transmitted over specialized a neural network to CNS
where it is interpreted as such.
- MaCbryde (1952)
pain is a disagreeable sensation produces by the action of stimuli
of humural nature

HISTORICAL NOTE :
Derived from Greek - ”Poin” meaning penalty.
Derived from Latin -“Poena” meaning punishment from God.
Homer thought pain was due to arrows shot by God. Aristotle, who
probably was the first to distinguish five physical senses considered pain to
the “passion of the soul” that somehow resulted form the intensification of
other sensory experience.
Plato contented pain and pleasure arose from within the body, an idea
that perhaps gave birth to the concept that pain is an emotional experience
more than a localized body disturbance. The Bible makes reference to pain
not only in relationship to injury and illness but also an anguish of the soul.
Hebrew words use to express grief, sorrow, and pain are used rather
interchangeably in old scripture.

THE EVOLUTION OF PAIN :

As knowledge of anatomy and physiology increased it became
possible to distinguishing between pain due to physical and emotional
causes. During the 19th century, the developing field to neurology fostered
the concept that pain was mediated.

CHANGING CONCEPTS OF PAIN:

The definition of pain found in the medical dictionary summarizes
very well the traditional understanding of what pain is like “a more or less
localized sensation of discomfort, stress, or agony, resulting from the
stimulation of specialized nerve endings. It serves as a protective
mechanism insofar as it induces the sufferer to remove or withdrew from the
source.” This definition identifies pain a localized sensation that occurs as
the result of noxious stimulation.
During resent years, a quite different concept has evolved. Although
pain is now recognized as being more an experience than a sensation, it dose
have a sensory dimension that registers the nature of the initiating stimulus,
including its quality, intensity, location, and duration. But it has other
dimensions also:

1) Cognitive – Which represents the subject’s ability to comprehend

and evaluate the significance of the experience.
2) Emotional – Which represents the feelings that are generated and
3) Motivational – Which has to do with the drive to terminate it.
 More precisely, pain as presently conceived has a sensory-
discriminative dimension to identify the form of energy (thermal,
mechanical, and chemical) and the spatial, temporal, and intensive aspects
of the stimulus. It also has a motivational-effective property by which the
consequences of the experience manifest as escape and avoidance behavior,
which includes reflex somatic and automatic motor responses.

PAIN RECEPTORS :
Sensory Receptors :
Sensory input from various external stimuli is thought to be received
by specific peripheral receptors that act as transducers and transmit by nerve
action potentials along specific nerve pathways toward the central nervous
system. Termed first–order afferents, these peripheral terminals of afferent
nerve fibers differ in the form of energy to which they respond at their
respective lowest stimulus intensity, that is, are differentially sensitive. The
impulse is interpreted is nociceptive (causing pain) if it exceeds the pain
threshold, that is, the intensity of the stimulus is so great that the receptor is
not longer differentially sensitive.
Cutaneous Receptors :
The perception of different kinds of sensation has demonstrated the
existence of sensory spots in the skin. These sensory spots are thought to
contain receptors which are distinguished by the from of stimulus that
excites them and their location within the skin, and are distinguished
morphologically as corpuscular and noncorpuscular.
The pacinian corpuscles, in particular, are highly sensitive
mechanoreceptors which respond to rapid mechanical changes, and are
especially responsive to vibration. Other mechanoreceptors are the Meissner
corpuscles, Golgi – Mazzoni corpuscles, Ruffini’s ending, and Krause bulb.
Although, electron microscopy has defined the presence of many receptors
structurally, functionally three categories of cutaneous receptors are thought
to exist : mechanoreceptors, thermo receptors, and nociceptors.
Pain receptors are ‘free’ nerve endings i.e., they are not enclosed in a
capsule. The receptors for fast pain are sensitive to mechanical or thermal
stimuli of noxious strength. The receptors for slow pain are sensitive not
only to noxious mechanical and thermal stimuli but also to a wide variety of
chemicals associated with inflammation. These substances include
histamine, serotonin, bradykinin, acetylcholine, potassium ions and
hydrogen ions. It is possible that noxious mechanical and thermal stimuli
also act through the release of some of these chemicals. Since pain receptors
respond to a wide variety of stimuli, they are called polymodal. Since all the
stimuli to which pain receptors respond are potentially damaging, or
noxious, these receptors are also called nociceptors. Although nociceptors
are polymodal, they are specific receptors completely dedicated to
conveying pain through specific neural pathways. Pain receptors completely
dedicated to conveying pain through specific neural pathways. Pain
receptors adapt rather poorly to a prolonged stimulus. That is why a pain
may be felt almost continuously for weeks or months. Pain receptors are
found maximally in the skin, but significant numbers are also present in the
periosteum, arterial walls, joint surfaces, falx cerebri and the tentorium.
Deep viscera are rather poorly supplied by pain receptors. However, fast
pain receptors are present only in the skin. That is why only pain originating
in the skin is well localized. The most conspicuous part of the body which
has no pain receptors at all is the brain. That is why a neurosurgeon can
work on the brain after infiltration of the extra cranial tissues with a local
anaesthetic. It is paradoxical that the organ which perceives pain cannot
itself detect any painful stimulus.
NEUROCHEMISTRY OF NOCICEPTIVIE PAIN :
The peripheral nociceptor can be activated by thermal, mechanical,
and chemicals stimulation. When thermal and mechanical stimulation
produce nociceptive input, the reason for the pain is usually apparent. There
are a variety of compounds that can accumulate near the nociceptor
following tissue injury that can be responsible for maintaining nociceptive
input. There are at least three sources of these compounds: the damaged
cells themselves, secondary to plasma extravasation and lymphocyte
migration, or the nociceptor itself.
Damage to tissue cells produces leakage of intracellular contents.
Among the substances released by tissue damage are potassium and
histamine, both of which either activate or sensitize the nociceptor. These
substance have been documented to excite polymodal nociceptors and
produce pain when injected into skin. Other compounds such as
acetylcholine, serotonin, and ATP maybe released by tissue damage and are
known to either activate or sensitize nociceptors.
Bradykinin one of the most potent pain producing substances that appears in
injured tissue is bradykinin. Bradykinin is an endogenous polypeptide
consisting of a chain of nine amino acids. Released as part of an
inflammatory reaction, it is a powerful vasodilator and causes increased
capillary permeability. Bradykinin requires the presence of prostaglandins
act. It is also released during ischemic episodes. Polymodal nociceptors can
be activated by bradykinin and they then can become sensitized to thermal
stimuli.
Another group of compounds that are synthesized the regions of tissue
damage are the metabolic products of arachidonic acid. These compounds
are considered inflammatory mediators mediators and include both
prostaglandins and leukotrienes. These compounds appear whenever animal
cells are damaged and are present in increased concentration in
inflammatory exudates. The prostaglandins are a group of chemically
related long chain hydroxy fatty acids. There are six types, each designated
by a suffix latter. Prostaglandin E2 is metabolized from arachidonic acid
through the action of cyclo – oxygenase. This occurs in conjunction with an
inflammatory process.
Prostaglandins do not seem to be algogenic substances per se. they
sensitize nociceptive nerve endings to different type stimuli, thus lowering
their pain thresholds to all kinds of stimulation. Prostaglandins are required
for bradykinin to act, bradykinin in turn stimulates the release of
prostaglandins. The two therefore are naturally potentiating. Prostaglandin E
also increases the response of slowly adapting A – delta mechanoreceptors
to noxious stimuli. There is evidence that a prostaglandin like substance is
released in the CNS during an inflammatory reaction that induces
prostaglandin hyperalgesia.
Another important metabolic pathway of arachidonic acid is the lipo-
oxygenase pathway, which produces the leukotrienes. Leukotrienes produce
hyperlgesia in animal models and in humans.
In addition to the chemical mediators that are released form damaged
cells or synthesized in the region of damage, the nociceptors themselves can
release substances that enhance nociception. One such substance is
substance P. and, when stimulated, can release this potent excitatory
neurotransmitter into the extra cellular space. Substance P is a very strong
vasodilator and produces edema. Substance P also causes release of
histamine from mast cells, which is an excitatory neurotransmitter and also
causes vasodilatation and edema.

THEORIES OF PAIN :
It is often assumed that pain is a warning that damage has occurred.
But this is not strictly true. Because pain may occur when there is not
obvious disease as in the primary neuralgias and many diseases does not
cause pain, at least in the early stages. So these are various theories being
put forward on how nerve impulses give rise to sensation of pain.
1) Intensity theory
2) Specificity theory
3) Protopathic and Epicritic theory
4) Pattern theory
5) Gate control theory.
1) Intensity theory :
According to this theory pain is produced when any sensory nerve is
stimulated beyond a certain level. This theory states that if electric current
stimulates teeth ; threshold sensation is variously described as hot, cold,
tingling, etc, but if the intensity increases it gives sensation as pain. But the
trigeminal theory is an example, against this theory. In this cases patient
with trigeminal neuralgia exhibits pain from the stimulus no greater than the
general touch.
2) Specificity theory (Johnnes Muller, 1842) :
According to this theory, pain is a specific modality equivalent to
vision and hearing. Just as there are meissner corpuscles for touch, Ruffini
end organs for warmth and Krause end organ for cold, pain is mediated by
free nerve endings.
This theory states that a direct line form the receptor to the brain and
the stimulus at the receptor is necessarily followed by pain sensation. The
commonest on this theory is that, anyone who has suffered injury during an
exciting game and not noticed it until later. So for the specificity theory to
have been correct he would have felt considerable pain even though
sufficiently interested in the game.
This theory is also disapproved by the concept of trigeminal
tractotomy, which fails to abolish pain in that area instead pain becomes
worse, it is true because the direct line implied by the specificity theory can
be bypassed the impulses mediating pain being conveyed to higher center
via the reticular activating.
3) Protopathic and Epicritic theory :
Head and Rivers (1908) postulated the existence of two cutaneous
sensory nerves extending from the periphery to the CNS.
The protopathic system is primitive, yielding diffuse impression of
pain, including extremes of temperature and is upgraded. The epicritic
system is concerned with tough discrimination and small changes in
temperature and is phylogenetically a more recent acquisition.
4) Pattern theory (Goldscheider, 1894) :
This theory states that pain sensation depends upon spatio – temporal
pattern of nerve impulses reaching the brain.
According to Wodddell (1962) warmth, cold and pain are words used
to describe reproducible spatio – temporal pattern, or codes of neural
activity evoked from skin by changes in environment. The precise pattern of
nerve impulse entering the CNS will be different for different regions and
will vary from person to person because of normal anatomical variations.
5) Gate control theory :
In the year 1959 Noordenbos postulated that fast fibers (large) exert
as inhibiting effect on the slowly conducting fibers. It was Melzaek and
Wall (1965) came out with the concept of gate control. According to this
theory the small nerve fibers reach the dorsal horn of spinal cord and relay
impulses to further cells which transmit them to higher levels. The large
nerve fibers have collateral branches which carry impulse to substantia
gelatinosa (SG) where they stimulate the secondary neurons. These SG cells
terminate on the smaller nerve fibers thus reducing their activity. The result
is that on going activity is reduced or stopped altogether.
 Gate is closed. If for any reasons, the large nerve fibers carry fewer
impulses their modulating activity is reduced and the gate opens again. As
the large nerve fibers reach the cord they bifurcate, one branch going to SG,
the other branch passes into dorsal columns on the same side conveying
impulses to the dorsal column nuclei. From here they are relayed to the
thalamus and lines to the cerebral cortex.

FACTORS AFFECTING PAIN :

1. Emotional status :
The pain threshold depends greatly on attitude towards the procedure.
In case of emotionally unstable and anxiety patient the pain threshold is low
but reaction s high.
2. Fatigue :
Pain reaction threshold is high in subjects who has good night sleep
and relaxed, then those persons who are tired.
3. Age :
Older individuals tend to tolerate pain and thus have higher pain
reaction threshold than young individuals. Perhaps their philosophy of
living or the realization that unpleasant experiences are a part of life may
account for this fact.
4. Racial and nationally characteristics :
It has been said that racial characteristics are reflected in the pain.
The Causcasian and Negro races have little or no variation in the pain
reaction threshold. The Latin Americans and Southern Europeans are more
emotional than North Americans or Northern Europeans may be in warmer
climates tend to have lower pain reaction threshold.
5. Sex :
Men have higher pain threshold than women. This may be a reflection
of man’s desire to maintain his feeling of superiority and this is exhibited in
his pre determined effort to tolerate pain.
6. Fear and apprehension :
Most cases pain threshold is lowered as fear and apprehension
increases. Individuals who are extremely fearful tend to magnify their
experiences.

NEURAL PATHWAYS OF PAIN :

Field has described that the subjective experience of pain arises by
four distinct processes.
Transduction : If the process by which noxious stimuli leads to electrical
activity in the appropriate sensory nerve ending.
Transmission : It refers to neural event that carry the nociceptive input into
the central nervous system for proper processing.
Modulation : the neural impulse (nociceptive) are changed or altered before
reaching the higher centers (Cortex).
Perception : It determined by interaction of the (cortex, thalamus, and
limbic system) higher centers.

The first order neuron: Each sensory receptor is attached to a first order
primary afferent neuron that carries the impulses to the CNS. The axons of
these first-order neurons are found to have varying thickness. It has long
been known that a relationship exists between the diameter of nerve fibers
and their conduction velocities. The larger fibers conduct impulses more
rapidly than smaller fibers.
A general classification of neurons divides the larger fibers from the smaller
ones,
Type A fibers
1. Alpha fibers: size - 13 to 20 µm, velocity - 70 to 120 m/ s.
2. Beta fibers: size – 6 to 13 µm, velocity – 40 to 70 m/s.
3. Gamma fibers: size – 3 to 8 µm, velocity – 15 to 40 m/s.
4. Delta fibers: size – 1 to 5 µm, velocity – 5 to 15 m/s.
Type C fibers
Size – 0.5 to 1 µm, velocity – 0.5 to 2 m/s.
There also appears to be a relationship between fiber size and the type of
impulse transmitted, although strict specificity has not been proven. It
appears that the fast conducting A-alpha, A-beta, and A-gamma fibers
carry impulses that induce tactile and proprioceptive responses but not
pain. It seems that pain is conducted by A-delta and C-fibers, but these
are not specific for pain only.
There are three classes of nociceptive afferent neurons provide the input
whereby the brain perceives pain.
1) Mechanothermal afferents are primarily A-delta fibers that
conduct at a velocity of 12 to18 m/s and respond to intense
thermal and mechanical stimuli. They provide a degree of
discriminative information and are peculiar to primates.
2) Polymodal afferents are C fibers that conduct much more slowly,
at a velocity of 0.5 m/s, and respond to mechanical, thermal, and
chemical stimuli.
3) High- threshold mechanoreceptive afferents are chiefly A –delta
fibers and normally respond to intense mechanical stimuli in all
mammals.
Second-Order Neuron
The primary afferent neuron carries impulse into the CNS and
synapses with the second-order neuron. This second-order neuron is
sometimes called a transmission neuron since it transfers the impulse on to
the higher centers. The synapse of the primary afferent and the second-order
neuron occurs in the dorsal horn of the spinal cord.

PAIN PATHWAYS:
When a peripheral nerve is stimulated, a series of events occur that carry
that impulse into the CNS and to the higher centers for interpretation and
evaluation. If the impulse has significance, the higher centers may pass it to
the cortex where it is then perceived as pain. This series of events is by no
means simple. In fact most of the impulses that enter the CNS never reach
the cortex. To better understand orofacial pains, we will now follow the
pathway of a nociceptive impulse from the peripheral receptor to the cortex.
It would be easy to believe that orofacial nociception begins with a
trigeminal nerve pathway. Although this is commonly true, it is only one of
many pathways that carry orofacial nociception to the brain. Nociceptive
impulses from the face and mouth may be mediated centrally by way of
afferent primary neurons that pass through the 5 th, 7th, 9th, and 10th cranial
nerves as well as the 1st, 2nd, and 3rd cervical spinal nerves and by way of
visceral afferents that descend through the cervical sympathetic chain to
pass through the posterior roots of the upper thoracic spinal nerves.
To simplify our discussion, we will only discuss the pathway of a single
trigeminal primary afferent neuron, for example, coming from the pulp of a
mandible molar. Once the nociceptor located in the pulp is activated, the
impulse is carried into the central nervous system by a primary afferent
neuron in the mandibular branch of the 5th cranial nerve. The cell bodies of
this nerve are located in the gasserian ganglion. This primary neuron enters
the brain stem and synapses with a second order neuron in the subnucleus
caudalis of the trigeminal spinal tract nucleus. This second order nociceptive
specific (NS) neuron then be activated and the impulse will be carried to the
higher centers by this neuron. In some instances, the neuron may carry the
impulse directly on the same side of the brain. This is not usually the case
with nociception. In most instances, the NS neuron will cross the brain stem
and ascend in the anterolateral tract on the opposite side. At this point
nociceptive input can be carried by one of two tracts they are;
1)Neospinothalamic tract : Fast pain is conducted to the spinal cord by A –
delta type of nerve fibers which have a conduction velocity f 6 – 30 m / s.
These fibers belong to neurons, the cell bodies of which lie in dorsal root
ganglia. The central axons of these neurons terminate mainly in lamina I,
but also in laminae II and V of the dorsal horn of the spinal cord. There they
synapse with projection neurons which continue as the neospinothalamic
tract on the contralateral side. On their way to the thalamus,
neospinothalamic fibers give off collaterals in the reticular formation,
tectum and the periaqueductal gray (PAG). In the thalamus,
neospinothalamic fibers relay in the ventrobasal complex. The arrangement
of neurons in the ventrobasal complex is topographic (i.e., in terms of
location of he stimulus on the body), not in terms of the modality of the
stimulus (i.e., whether it is touch or pain or temperature). Hence the
ventrobasal complex provides the first station where all types of stimuli
from a given part of the body relay in neighbouring neurons. The thalamic
neurons project to the sensory cortex in a topographic manner and re
-organized in modality specific columns. However the columns dedicated to
pain are far fewer than those to touch. That is why pain itself is not as
accurately localized as touch. But since painful stimuli are frequently linked
to simultaneous stimulation of touch receptors, the sensation of touch aids
the localization of painful stimulus. Perhaps that is one way by which
moving the finger over a tender area helps in better localization of the tender
spot.
2) Paleospinothalamic tract : Slow pain is conducted to the spinal cord by
C type of nerve fibers which have a conduction velocity of 0.52 m / s. This
information is conveyed to the dorsal horn of the spinal cord mainly in
lamina II (substantia gelatinosa). The projection neurons for slow pain travel
in the paleospinothalamic tract. Paleospinothalamic fibers give off much
more collaterals in the reticular formation, tectum and PAG than the
neospinothalamic fibers. In the thalamus, paleospinothalamic fibers relay in
the nonspecific nuclei (i.e., midline and intralaminar nuclei). That is why
slow pain is poorly localized, and has a greater potential for keeping us
awake.

MODULATION OF PAIN :
Noxious stimuli of comparable intensity may produce varying
degrees of pain in the same individual under different circumstances. For
example, an injury acquired by an athlete in the sport field or by a soldier in
the battlefield is less painful than a comparable injury suffered in a road
accident. In other words, pain can be modulated. A plausible explanation for
modulation of pain was proposed in the 1960s by Ronald Melzack and
Patrick Wall in the form of gate control theory.
Gate Control Theory :
Gate control theory emphasized modulation of pain at the spinal cord
level by the simultaneous presence of non-noxious stimuli. Suppose a touch
stimulus is applied to the same area of skin which has been subjected to a
noxious stimulus. It was proposed that the touch fiber gave collateral in the
substantia gelatinosa of the dorsal horn of the spinal cord which, in turn,
inhibited the pain fiber presynaptically through an inhibitory interneuron.
That is how a touch stimulus could reduce the painfulness of a noxious
stimulus. The inhibitory interneuron acts as a gate. When it is activated, the
gate is closed, an pain impulses cannot ascend upwards. When the gate
neuron is inactive, pain impulses can ascend upwards and reach the sensory
cortex to make us conscious of the pain.
The theory appeals to commonsense because it is a general
experience that the presence of other competing stimuli reduces the ferocity
of pain. For example, generating a strong sensation over a painful joint by,
application of a counterirritant balm or cream reduces the pain. In general,
pains are felt more acutely at night when competing (or distracting) stimuli
are absent than during the day. While the gate control theory seems to
explain some of these observations, experimental studies have filed to find
evidence for the theory. However, the theory did stimulate much research on
modulation of pain and contributed to the discovery of an endogenous pain
relief system.
Endogenous Pain Relief System :
The body has an in-built system for reducing the intensity of pain.
Evidence for an endogenous pain relief system has been gathered during the
past twenty years from a variety of studies. Stimulation of several areas of
the central nervous system produces a specific analgesic response. The most
important among these areas is the periaqueductal gray (PAG). Receptors
for morphine and similar substances (opioid receptors) are present in all the
major relay stations concerned with pain. i.e., substantia gelatinosa, reticular
formation, PAG and intralaminar thalamic nuclei, as well as throughout the
limbic system, which is concerned with pain, pleasure and visceral
functions. Further, substances resembling morphine in their molecular
configuration (endorphins) have been found to serve as neurotransmitters in
areas of the brain and spinal cord where opiod receptors are present.
Endorphins are also released from the anterior pituitary in response to stress.
All the above observations put together point to an endogenous pain
relief system which possibly works as follows. As in other sensory systems,
there are descending fibers which parallel the ascending fibers. The
descending fibers converge in the PAG. Activation of PAG neurons releases
serotonin as a neurotransmitter in the substantia gelatinosa. Serotonin, in
turn, activates enkephalinergic interneurons. The enkephalinergic neurons
inhibit the projection neurons of the pain pathway that is how descending
fibers can modulate the intensity of pain. The next natural question is what
activates the endogenous analgesic system physiologically. It seems any
form of stress, specially the stress of pain, activates the analgesic system
through the limbic system. Thus pain tends to cure itself, as expressed by
the great Urdu poet, Ghazi “Inhrat–e–katra hai dariya mein fana ho jana.
Dard ka had se guzarna hai dawa ho jana” (Just as a drop of water gets lost
in a river, when pain crosses a limit, it cures itself).
Gate Control Theory Revisited :
The interneurons which inhibit projection neurons of his pain system
do exist in the spinal cord. But these inhibitory interneurons are not
activated by touch and other primary afferents as postulated by the gate
control theory. Instead, the inhibitory interneurons seem to be activated by
the fibers descending form PAG and related areas. How, then can we
explain the modulation of pain by touch and other competing stimuli? The
dorsal column fibers, while ascending to the thalamus, give off collaterals to
the reticular formation. These collaterals could activate the descending
fibers of the endogenous analgesic system. Thus a touch stimulus can still
close the gate, although indirectly. Supporting this concept is the
observation that dorsal column stimulation often produces analgesia. The
effect is sometimes made use of by neurosurgeons to provide therapeutic
pain relief.

Referred pain:
Referred pain due to central sensitization is initially wholly
spontaneous as for as the site of pain concerned. It is not accentuated by
provocation of the site where the pain is felt, it is accentuated only by
manipulation of the primary pain source. It is dependent on continuance of
the primary initiating pain, it ceases immediately if the primary pain is
arrested or interrupted. Anesthesia of the structure where the referred pain is
felt does not arrest the pain. It should be noted that although the primary
initiating pain is of the deep somatic type, the secondary referred pain may
be felt in either deep or superficial structures.
Referred pain does not occur haphazardly but in fact follows three clinical
rules,
1. Referred pain frequently occurs within a single nerve root, passing
from one branch to another. Eg. Mandibular molar presenting with a
source of pain will commonly refer pain to a maxillary molar. This is
fairly common occurrence with dental pain. Generally, if the pain is
referred to another distribution of the same nerve, it does so in a
laminated manner. This lamination follows dermatomes. Trigeminal
lamination patterns are determined by the manner in which the
primary afferent neurons enter in the spinal tract nucleus. According
to Kunc, the location of the trigeminal nociceptieve terminals within
the nucleus caudalis ids as follows:
a) Fibers from parts near the saggital midline of the face terminate
highest in the nucleus (cephlad).
b) Fibers from parts located more laterally terminate lowest in the
nuleus (cauded).
c) The intermediate fibers terminate intermediately in the nucleus.
This grouping of the terminals of the primary trigeminal neurons should
influence the location of clinical effects of central excitation, a molar tooth
projects dorsal to canine projects dorsal to an incisor, which confirms the
vertical lamination just cited. This means incisors refer to incisors,
premolars to premolars, and molars to molars on the same side of the mouth.
In other words, molars do not refer pain to incisors or incisors to molars.
2) The referred pain in the trigeminal area rarely crosses the midline unless,
it originates at the midline. for example, pain in the right
temporomandibular joint will not likely cross over to the left side of the face
nor will right molar pain refer to a left molar. This is not true in the
cervicospinal region or below, cervicospinal pain can be referred across the
midline, although it normally stays on the same side as the source.
3) If referred pain is felt outside the nerve that mediates the pain, it is
generally felt cephalad to the nerve (upward, toward the head) and not
caudally. Clinically this means that deep pain felt in the sacral area maybe
referred to the lumbar area, as well as lumbar to thoracic, thoracic to
cervical, and cervical to trigeminal.

Secondary hyperalgesia (SH) : hyperalgesia is defined as increased

sensitivity to stimulation at the site of a lowered pain threshold in the
peripheral structures due presumably to the presence of algogenic
substances such as bradykinin, potassium, histamine, and serotonin. SH is
different, it is an increased response to stimulation at the site of pain in the
absence of any local cause. It may occur with or without accompanying
referred pain. Secondary hyperalgesia is also different from referred pain in
that it occurs in response to stimulation at the site of pain, while referred
pain cannot be increased at the site of pain. It is wholly dependent on the
source of pain. Both referred pain and secondary hyperalgesia are initiated
by deep pain input and remain dependent on the continuance of such input.
They differ, whoever in that secondary hyperalgesia persists for a while
after the primary pain ceases.
As with referred pain is felt in either superficial or deep structures. There
are two explanations for the occurrence of secondary hyperalgesia. The first
is that related to the sensitization of the second order neuron. Second,
central sensitization occurs even normal input can be misinterpreted as
noxious. Therefore, even input carried by the A-delta fibers (nonnoxius) can
be felt as pain. A second explanation for secondary hyperalgesia is a local
cause produced by neurogenic inflammation. With central sensitization, the
primary afferent neuron can create an antidromically produced neurogenic
inflammation.

There are two other related phenomena involving wrong interpretation of

pain. If pain fibers are stimulated mechanically or electrically on their way
to the spinal cord, the brain still interprets the pain as originating in the part
of the body where the corresponding nociceptors are located. For example,
if the pain fibers traveling in the ulnar nerve are stimulated at the elbow, the
pain is still perceived to originate in the hand. This phenomenon is called
projected pain. Another phenomenon, similar in its mechanism to projected
pain, is phantom pain. Following the amputation of limb, the cut ends of
severed nerves innervate the skin covering the stump. Stimuli existing the
nerve fibers at the stump are interpreted as originating in the limb which
does not exist any more. The phantom limb sometimes also experiences
pain, which is known as phantom pain. This phenomenon is basically
because the brain has been interpreting signals conveyed by those nerve
fibers as coming from the lost limb.

CONCLUSION :
Pain is bad, but not feeling pain can be worse. Individuals with a
congenital absence of pain receptors are extremely rare but not unknown.
Such individuals are very poor at avoiding accidental injuries, and often
inflict mutilating injuries on themselves. As a result, their life span is
usually short. thus pain, although unpleasant, is a protective sensation with
enormous survival value. Pain is a multidimensional experience involving
both the sensation evolved by noxious stimuli but also the relation to it. The
sensation of pain therefore depends in part on the patient past experience,
personality and level of anxiety.
Every day patient seeks care for the reduction or elimination of pain.
Nothing is more satisfying to the clinician than the successful elimination of
pain. The most important part of managing pain is understanding the
problem and cause of pain. It is only through proper diagnosis that
appropriate therapy can be selected.

REFERENCES :
1. Bell`s ‘Orofacial pain’, 5th edition, Jeffrey P. Okeson.
2. Text book of Medical Physiology, 2nd edition, Chaudhari.
3. Text book of Medical Physiology, 10th edition, Arther C Gyton.
4. Dental Clinics of North America 1978: 22 (1); 1-61.
5. Text book of ‘Oral medicine’- 10th edition, Burket’s.
6. Gray's Anatomy – 38th Edition, Churchill Eivingstone.
7. Understanding “Medical physiology”- 3rd edition, R L Bijlani.
8. Text book of Physiology – 3rd edition, Robert m. Bern, Mathew N.
Levy, Bruce M. Koeppen, Bruce A. Stanton.