The document summarizes the physiology of pain. It discusses how pain is a complex experience involving nociception and pain behaviors. It defines acute and chronic pain and describes the different pain fiber types and receptors. The gate control theory of pain is also summarized, which proposes that large diameter fibers can inhibit pain transmission while small fibers facilitate it through a "gate" in the spinal cord.

1. PHYSIOLOGY OF PAIN
Presented By
Siddhanta Choudhury
1st Year P.G
Dept. of Anaesthesiology
Guided By
Dr. B.K Panda
Asst. Professor
Dept. of Anaesthesiology

2.  Pain is perfect misery, the worst of evils; and excessive,
overturns all patience.
–John Milton, Paradise Lost

3.  The word pain is derived from the latin word poena
meaning penalty.
 Pain is not a simple sensation but rather a complex
neurobehavioral event involving at least two components.
 First is an individual’s discernment or perception of the
stimulation of specialized nerve endings designed to
transmit information concerning potential or actual tissue
damage (nociception).
 Second is the individual’s reaction to this perceived
sensation (pain behaviour).

4.  The difficulty to define, quantify and understand pain is
reflected in the numerous ways in which it has been
described
 Dorland’s Medical Dictionary defines pain as “a more or less
localized sensation of discomfort, distress, or agony
resulting from the stimulation of specialized nerve endings.”

5. DEFINITION OF PAIN
 International Association for the Study of Pain (IASP)
“An unpleasant sensory and emotional experience associated
with actual or potential tissue damage, or described in terms
of such damage.”

6.  Pain is always subjective.
 Each individual learns the application of the word through
experiences related to injury in early life.
 It is unquestionably a sensation in a part of the body, but it
is also always unpleasant and therefore also an emotional
experience.

7.  Many people report pain in the absence of tissue
damage or any likely pathophysiological cause.
 Usually this happens for psychological reasons.
There is no way to distinguish their experience from
that due to tissue damage, if we take the subjective
report.
 If they regard their experience as a pain and if they
report it in the same way as pain caused by tissue
damage, it should be accepted as pain.

8. CLASSIFICATION OF PAIN
► CLINICAL
► ACUTE PAIN
► Primarily due to nociception
► May be somatic or visceral
► CHRONIC PAIN
► May be due to nociception, but psychological and behavioural factors also play a
major role.
► PHYSIOLOGICAL
► Fast Pain
► Slow Pain

9. ACUTE PAIN
Caused by noxious stimulation due to injury, a disease process, or the abnormal function of muscle or
viscera
Four physiological processes are involved: transduction, transmission, modulation, and perception
Two types of acute (nociceptive) pain—somatic and visceral—are differentiated based on origin and
features.
Somatic pain —Somatic pain can be further classified as superficial or deep.
Superficial somatic pain is due to nociceptive input arising from skin, subcutaneous tissues, and mucous
membranes.
Deep somatic pain arises from muscles, tendons, joints, or bones.

10. Visceral pain —Visceral acute pain is due to a disease process or abnormal function involving an internal
organ or its covering (e.g., parietal pleura, pericardium, or peritoneum).
Four subtypes are described: (1) true localized visceral pain, (2) localized parietal pain, (3) referred visceral pain,
and (4) referred parietal pain.
It is frequently associated with abnormal sympathetic or parasympathetic activity causing nausea, vomiting,
sweating, and changes in blood pressure and heart rate.
The phenomenon of visceral or parietal pain referred to cutaneous areas results from patterns of
embryological development and migration of tissues, and the convergence of visceral and somatic afferent
input into the central nervous system.

11. CHRONIC PAIN
Chronic pain is pain that persists beyond the usual course of an acute disease or after a
reasonable time for healing to occur; this healing period typically can vary from 1 to 6
months.
Chronic pain is defined by the American Society of Anesthesiologists as “extending in
duration beyond the expected temporal boundary of tissue injury
and normal healing, and adversely affecting the function or well-being of the individual.”
The IASP subcommittee on taxonomy defined it in 1986 as “pain without apparent
biological value that has persisted beyond the normal tissue healing time usually taken to
be three months.”
Chronic pain may be nociceptive, neuropathic, or mixed.
A distinguishing feature is that psychological mechanisms or environmental factors
frequently play a major role.

12. SLOW PAINFAST PAIN
Felt within about 0.1 second after a pain
stimulus is applied.
Fast pain is also described by many
alternative names, such as sharp pain,
pricking pain, acute pain, and electric pain.
Generally elicited by mechanical & thermal
types of stimuli.
Not felt in deeper tissues
Begins only after 1 second or more and then
increases slowly over many seconds and
sometimes even minutes
Slow pain also goes by many names, such as
slow
burning pain, aching pain, throbbing pain,
nauseous pain, and chronic pain.
This type of pain is usually associated with tissue
destruction. It can lead to prolonged, almost
unbearable suffering.
Slow pain can occur both in the skin
and in almost any deep tissue or organ.

13. PAIN RECEPTORS
 The pain receptors in the skin and other tissues are all free nerve endings.
 The receptors which mediate pain are called NOCICEPTORS.
 small unmyelinated ‘C’ fibres or myelinated ‘A δ’ afferent neurons.
 widespread in the superficial layers of the skin as well as in certain internal
tissues, such as the periosteum, the arterial walls, the joint surfaces, and the falx
and tentorium in the cranial vault.

14. The peripheral pain fibers – ‘Fast’ and
‘slow’ fibers
FAST PAIN FIBERS SLOW PAIN FIBERS
fast sharp pain signals are
elicited by either mechanical or
thermal pain stimuli;
slow-chronic type of pain is
elicited mostly by chemical
stimuli but sometimes by
persisting mechanical or
thermal stimuli.
transmitted in the peripheral
nerves by small type Aδ fibers
transmitted to the spinal cord
by type C fibers
velocities between 6-30 m/s velocities between 0.5-2 m/s.

15. Fiber Diameter (µ) Conduction velocity (m/s) Function
A-alpha
A- beta
A-delta
A- gamma
B
C
6-20
5-12
1-4
3-6
< 3
0.4-1.0
30-120 (myelinated)
30-120
5-25
15-35
3-15 (myelinated)
0.7-2.0 (unmyelinated)
Motor, perception
Motor, perception
Pain, temperature, touch
Muscle tone
Various autonomic functions
Various autonomic functions;
pain temperature, touch

16. NONADAPTING NATURE OF PAIN RECEPTORS
In contrast to most other sensory receptors of the body, pain receptors adapt very little
and sometimes not at all.
Under some conditions, excitation of pain fibers becomes progressively greater,
especially for slow-aching-nauseous pain, as the pain stimulus continues.
This increase in sensitivity of the pain receptors is called hyperalgesia.
One can readily understand the importance of this failure of pain receptors to adapt
because it allows the pain to keep the person apprised of a tissue-damaging stimulus as
long as it persists.

17. TYPES OF STIMULI THAT EXCITE PAIN
RECEPTORS
 Pain can be elicited by multiple types of stimuli.
 They are classified as mechanical, thermal, and chemical pain
stimuli.
 fast pain is elicited by the mechanical and thermal types of
stimuli
 slow pain can be elicited by all three types.

18. Chemical mediators
 Some of the chemicals that excite the chemical type of pain are
bradykinin, serotonin, histamine, potassium ions, acids, acetylcholine,
and proteolytic enzymes.
 The most important of these peptides are substance P and calcitonin
gene-related peptide (CGRP). Glutamate is the most important excitatory
amino acid.

19. Nociceptors
sensitized by
Nociceptors
activated by
o Bradykinin
o Histamine
o Serotonin
o Increased potassium
concentration
o Proteolytic enzymes
o Acids
o Acetlycholine
o Prostaglandins
o Substance P
o Interleukins
o Leukotrienes

20. Chemical mediators of pain

22. Special Importance of Chemical Pain Stimuli During Tissue Damage
 Extracts from damaged tissue cause intense pain when injected beneath the normal skin.
 One chemical that seems to be more painful than others is bradykinin.
 Researchers have suggested that bradykinin might be the agent most responsible for causing pain
after tissue damage.
 Also, the intensity of the pain felt correlates with the local increase in potassium ion concentration
or the increase in proteolytic enzymes that directly attack the nerve endings and excite pain by
making the nerve membranes more permeable to ions.

23.  Damaged tissue or blood cells release the polypeptide bradykinin
(BK), potassium, histamine, serotonin, and arachidonic acid.
 Arachidonic acid is processed by two different enzyme systems to
produce prostaglandins and leukotrienes, which, along with BK, act
as inflammatory mediators .
 Bradykinin acts synergistically with these other chemicals to increase
plasma extravasation and produce edema.
 Plasma extravasation, in turn, replenishes the supply of inflammatory
chemical mediators.

24. Tissue ischemia as a cause of pain
 When blood flow to a tissue is blocked, tissue becomes
painful within minutes.
 Accumulation of large amounts of lactic acid in the tissue
a consequence of anaerobic metabolism.
 It is also probable that other chemical agents, such as
bradykinin and proteolytic enzymes, are formed in the
tissues.

25. Muscle spasm as a cause of pain
 Partially from the direct effect of muscle spasm in
stimulating mechano sensitive pain receptors
 Also result from the indirect effect of muscle spasm to
compress the blood vessels and cause ischemia

26. Dual Nature of Pain
Pain has two components:
 Pain perception
 Pain reaction

27. PAIN PERCEPTION
Objective component of pain. Emotional experience to the perceived
injury.
Physio-anatomic process
Impulse is generated after application
adequate stimulus and is transmitted
the CNS.
Psycho physiological process and
involves the cortex, hypothalamus &
thalamus.
This aspect of pain is almost similar in
healthy individuals and varies little
day to day
Varies from individual to individual
also from day to day in the same
person.
PAIN REACTION

28.  SENSORY THRESHOLD- defined as the lowest level of stimuli
that will cause any sensation-the summation of large sensory
fibers from receptors for touch, temperature & vibration.
 PAIN THRESHOLD – As the stimulus is increased, the sensation
becomes stronger until pain is perceived. This is pain threshold.
 Fairly constant among individuals.

29. PAIN TOLERANCE / RESPONSE THRESHOLD
 If the intensity of the stimulus is increased above pain threshold, a
of pain will be reached that the subject can no longer endure. This is
pain tolerance or the response threshold.
 At this point the individual makes an attempt to withdraw from the
stimulus.
 Range between the pain threshold and the response threshold is
termed as a person’s tolerance to pain.

30. Theories of pain perception
 Specificity theory
1890s von Frey
 Central Summation theory
Livingstone 1943
 Sensory-Interaction theory
Noordenbos 1959
 Gate Control Theory
Ron Melzack and Patrick Wall 1965

31. Specificity theory
 This theory advocated the concept that different sensory fibers
mediate different sensory modalities such as pain, touch, cold,
pressure and heat.
 Free unmyelinated nerve endings were implicated as the pain
receptors. When stimulated, these fibers transmitted impulses
along specific pathways.
 A pain center was thought to exist in the brain - responsible for
all the manifestations of pain.

32. Central Summation theory
 Also known as Intensity theory
 This theory suggested that the stimulus intensity and central
summation were the critical determinants of pain
 Pain is not a separate modality but results from overstimulation of
other primary sensations.
 Excessive stimulation activated all types of receptors resulting in
convergence and summation of activity in the brain stem and spinal
cord.
 Pain resulted when activity exceeded a critical level normally responsive
to non-noxious stimuli.

33. Sensory-Interaction theory
It describes two systems involving transmission of pain: fast and slow system. The latter
presumed to conduct somatic and visceral afferents whereas the former was considered
to inhibit transmission of the small fibers.
 Rapidly-conducting large fiber pathways inhibit activity in slowly conducting small
fiber pathways that convey noxious information.
 An increase in the ratio of large to small fiber activity results in more inhibition in
nociceptive pathways and a decrease in pain.
 It stressed the importance of multi synaptic afferent system in the spinal cord.

34. Gate Control Theory
 Combined the strengths of previous theories and added some of its own.
 According to his theory, pain stimulation is carried by small, slow fibers that enter
the dorsal horn of the spinal cord; then other cells transmit the impulses from the
spinal cord up to the brain.
 These fibers are called T-cells. The T-cells are located in a specific area of the spinal
cord, known as the substantial gelatinosa. These fibers can have an impact on the
smaller fibers that carry the pain stimulation.
 In some cases they can inhibit the communication of stimulation, while in other
cases they can allow stimulation to be communicated into the central nervous
system.
 For example, large fibers can prohibit the impulses from the small fibers from ever
communicating with the brain. In this way, the large fibers create a hypothetical
"gate" that can open or close the system to pain stimulation.
 According to the theory, the gate can sometimes be overwhelmed by a large
number of small activated fibers. In other words, the greater the level of pain
stimulation, the less adequate the gate in blocking the communication of this
information.

35.  There are 3 factors which influence the 'opening and closing' of the gate:
 The amount of activity in the pain fibers. Activity in these fibers tends to open the
gate. The stronger the noxious stimulation, the more active the pain fibers.
 The amount of activity in other peripheral fibers—that is, those fibers that carry
information about harmless stimuli or mild irritation, such as touching, rubbing,
or lightly scratching the skin. These are large-diameter fibers called Aβ fibers.
Activity in Aβ fibers tends to close the gate, inhibiting the perception of pain
when noxious stimulation exists. This would explain why gently massaging or
applying heat to sore muscles decreases the pain.
 Messages that descend from the brain: Neurons in the brainstem and cortex have
efferent pathways to the spinal cord, and the impulses they send can open or
close the gate. The effects of some brain processes, such as those in anxiety or
excitement, probably have a general impact, opening or closing the gate for all
inputs from any areas of the body. But the impact of other brain processes may
be very specific, applying to only some inputs from certain parts of the body. The
idea that brain impulses influence the gating mechanism helps to explain why
peopie who are hypnotized or distracted by competing environmental stimuli
may not notice the pain of an injury.

36.  The basic points put forth by the theory are as follows:
 The term “gate” only refers to the relative amount of inhibition or
facilitation that modulates the activity of the transmission cells carrying
information about noxious stimuli
 there is a "gating system" in the central nervous system that opens
and closes to let pain messages through to the brain or to block them
 large diameter (Aβ) fibers activated by low threshold non-noxious
stimuli, and small-diameter (Aδ + C) fibers activated in most cases by
intense, noxious stimuli.
 Activity in large fibers tends to inhibitt transmission (close the gate)
 Small fiber activity tends to facilitate transmission (open the gate).

37.  Final response - depends on the net result of the initial input from all 3
systems
1) Large diameter fibers
2) Small diameter fibers
3) Central Control
 Thin fibres activity impedes the inhibitory cells (allow the transmission cell to
transmit signal)
 Large diameter fibre activity excites the inhibitory cell (inhibiting transmission
cell activity)
 More the large fibre activity (touch, pressure) relative to thin fibre activity at
inhibitory cells, less pain is felt.

38. MECHANISM OF GATE CONTROL
THEORY

39. Processing of pain from the stimulation of primary
afferent nociceptors to the subjective experience of
pain can be divided into 4 steps
1) Transduction
2)Transmission
3) Modulation
4) Perception

40. Pain processing

41. TRANSDUCTION
 Activation Of The Primary Afferent Nociceptor.
 Can Be Activated By Intense Thermal & Mechanical Stimuli,
Noxious Chemicals And Noxious Cold.
 Also Activated By Stimulation From Endogenous Algesic
Chemical Substances.
 Increases plasma extravasation & produces edema.
 Replenishes supply of inflammatory mediators
 Causes release of prostaglandins.

42. TRANSMISSION
 the process by which peripheral nociceptive information is relayed to the central
nervous system.
 Pain is conducted along three neuronal pathways that transmit noxious stimuli
from the periphery to the cerebral cortex
 The cell bodies of primary afferent neurons are located in the dorsal root ganglia,
which lie in the vertebral foramina at each spinal cord level.
 First-Order Neurons
 The majority of first-order neurons send the proximal end of their axons into the spinal
cord via the dorsal (sensory) spinal root at each cervical, thoracic, lumbar,and sacral
level
 Once in the dorsal horn, in addition to synapsing with second-order neurons, the axons
of fi rst-order neurons may synapse with interneurons, sympathetic neurons, and ventral
horn motor neurons.
 Pain fibers originating from the head are carried by the trigeminal (V), facial (VII),
glossopharyngeal(IX), and vagal (X) nerves.

43.  Second-Order Neurons
 As afferent fibers enter the spinal cord, they segregate according to size, with
myelinated fibers becoming medial, and small, unmyelinated fibers becoming
lateral.
 Pain fibers may ascend or descend one to three spinal cord segments in Lissauer’s
tract before synapsing with second-order neurons in the gray matter of the
ipsilateral dorsal horn.
 In many instances they communicate with second-order neurons through
interneurons
 Second-order neurons are either nociceptive-specific or wide dynamic range
neurons. Nociceptive- specific neurons serve only noxious stimuli, but WDR
also receive non-noxious afferent input from Aβ, Aδ, and C fibers.
 Nociceptive-specific neurons are arranged somatotopically in lamina I and have
discrete, somatic receptive fields; they are normally silent and respond only to
threshold noxious stimulation, poorly encoding stimulus intensity.
 WDR neurons are the most prevalent cell type in the dorsal horn. Although they
found throughout the dorsal horn, WDR neurons are most abundant in lamina V.
During repeated stimulation, WDR neurons characteristically increase their firing
rate exponentially in a graded fashion (“wind-up”), even with the same stimulus
intensity. They also have large receptive fields compared with nociceptive specific
neurons.

44.  Most nociceptive C fibers send collaterals to, or terminate on, second-order
neurons in laminae I and II, and, to a lesser extent, in lamina V.
 In contrast, nociceptive Aδ fibers synapse mainly in laminae I and V, and, to a
lesser degree, in lamina X.
 Lamina I responds primarily to noxious (nociceptive) stimuli from cutaneous
and deep somatic tissues.
 Lamina II, also called the substantia gelatinosa, contains many interneurons
and is believed to play a major role in processing and modulating nociceptive
input from cutaneous nociceptors
 Visceral afferents terminate primarily in lamina V, and, to a lesser extent, in
lamina I. These two laminae represent points of central convergence between
somatic and visceral inputs.
 Lamina V responds to both noxious and nonnoxious sensory input and
receives both visceral and somatic pain afferents. The phenomenon of
convergence between visceral and somatic sensory input is manifested
clinically as referred pain

46.  The Spinothalamic Tract
 The axons of most second-order neurons cross the midline close to their dermatomal
of origin (at the anterior commissure) to the contralateral side of the spinal cord before
form the spinothalamic tract and send their fibers to the thalamus, the reticular formation,
the nucleus raphe magnus, and the periaqueductal gray.
 The spinothalamic tract, which is classically considered the major pain pathway, lies
anterolaterally in the white matter of the spinal cord.
 This ascending tract can be divided into a lateral and a medial tract. The lateral
spinothalamic (neospinothalamic) tract projects mainly to the ventral posterolateral
of the thalamus and carries discriminative aspects of pain, such as location, intensity, and
duration.
 The medial spinothalamic (paleospinothalamic) tract projects to the medial thalamus and
responsible for mediating the autonomic and unpleasant emotional perceptions of pain.
 Some spinothalamic fibers also project to the periaqueductal gray and thus may be an
important link between the ascending and descending pathways.
 Collateral fibers also project to the reticular activating system and the hypothalamus;
are likely responsible for the arousal response to pain

48. ALTERNATE PAIN PATHWAYS
 The spinoreticular tract is thought to mediate arousal and autonomic
responses to pain.
 The spinomesencephalic tract may be important in activating
antinociceptive, descending pathways, because it has some projections to
the periaqueductal gray.
 The spinohypothalamic and spinotelencephalic tracts activate the
hypothalamus and evoke emotional behavior.
 The spinocervical tract ascends uncrossed to the lateral cervical nucleus,
which relays the fibers to the contralateral thalamus; this tract is likely a
major alternative pathway for pain.
 Lastly, some fibers in the dorsal columns (which mainly carry light touch
and proprioception) are responsive to pain; they ascend medially and
ipsilaterally

49. INTEGRATION WITH THE SYMPATHETIC AND MOTOR
SYSTEMS
 Somatic and visceral afferents are fully integrated with the skeletal motor and
sympathetic systems in the spinal cord, brainstem, and higher centers.
 Afferent dorsal horn neurons synapse both directly and indirectly with anterior
horn motor neurons. These synapses are responsible for the reflex muscle
activity—whether normal or abnormal—that is associated with pain.
 In a similar fashion, synapses between afferent nociceptive neurons and
sympathetic neurons in the intermediolateral column result in reflex
sympathetically mediated vasoconstriction, smooth muscle spasm, and the
release of catecholamines, both locally and from the adrenal medulla.

50. Third-Order Neurons
 Third-order neurons are located in the thalamus and send fibers to
somatosensory areas I and II in the postcentral gyrus of the parietal
and the superior wall of the sylvian fissure, respectively.
 Perception and discrete localization of pain take place in these cortical
areas.
 Although most neurons from the lateral thalamic nuclei project to the
primary somatosensory cortex, neurons from the intralaminar and medial
nuclei project to the anterior cingulate gyrus and are likely involved in
mediating the suffering and emotional components of pain.

51. MODULATION
Refers to mechanisms by which the transmission of noxious information to
the brain is reduced or intensified.
 Peripheral Modulation of Pain
Nociceptors and their neurons display sensitization following repeated stimulation. Sensitization
may be manifested as an enhanced response to noxious stimulation or a newly acquired
responsiveness to a wider range of stimuli, including nonnoxious stimuli.
Pain due to a stimulus that does not normally provoke pain(Allodynia) e.g. normal tactile or
thermal stimuli becoming painful.
Increased pain from a stimulus that normally provokes pain(Hyperalgesia)
 A. Primary Hyperalgesia
It is hyperalgesia at the original site of injury.
Sensitization of nociceptors results in a decrease in threshold, an increase in the frequency of
response to the same stimulus intensity, a decrease in response latency, and spontaneous firing
even after cessation of the stimulus (afterdischarges ).
Such sensitization commonly occurs with injury and following application of heat. Primary
hyperalgesia is mediated by the release of noxious substances from damaged tissues.

52. Secondary Hyperalgesia
Hyperalgesia in the uninjured area surrounding the injury
Enhanced pain response to only mechanical stimuli.
Neurogenic inflammation plays an important role in peripheral sensitization
following injury.
It is manifested by the “triple response (of Lewis)” of a red flush around the site
of injury (flare), local tissue edema, and sensitization to noxious stimuli.
Secondary hyperalgesia is primarily due to antidromic release of substance P
(and probably CGRP)

55.  Central Modulation of Pain
 Facilitation
At least three mechanisms are responsible for central sensitization in the spinal
cord:
1. Wind-up and sensitization of second-order neurons. WDR neurons increase
their frequency of discharge with the same repetitive stimuli and exhibit
prolonged discharge, even after afferent C fiber input has stopped.
2. Receptor field expansion. Dorsal horn neurons increase their receptive fields
such that adjacent neurons become responsive to stimuli (whether noxious or
not) to which they were previously unresponsive.
3. Hyperexcitability of flexion reflexes. Enhancement of flexion reflexes is
both ipsilaterally and contralaterally.
Neurochemical mediators of central sensitization include substance P, CGRP,
vasoactive intestinal peptide (VIP), cholecystokinin (CCK), angiotensin, and
as well as the excitatory amino acids l-glutamate and l-aspartate.

56.  Inhibition
 Transmission of nociceptive input in the spinal cord can be inhibited by segmental
activity in the cord itself, as well as by descending neural activity from supraspinal
centers.
1. Segmental inhibition
Activation of large afferent fibers subserving sensation inhibits WDR neuron and
spinothalamic tract activity. Moreover, activation of noxious stimuli in noncontiguous parts of
the body inhibits WDR neurons at other levels, which may explain why pain in one part of
body inhibits pain in other parts. These two phenomena support a “gate” theory for pain
processing in the spinal cord.
Glycine and γ-aminobutyric acid (GABA) are amino acids that function as inhibitory
neurotransmitters and likely play an important role in segmental inhibition of pain in the
spinal cord.
Antagonism of glycine and GABA results in powerful facilitation of WDR neurons and
produces allodynia and hyperesthesia.
There are two subtypes of GABA receptors: GABAA & GABA B. Segmental inhibition
to be mediated by GABA B receptor activity.
Adenosine also modulates nociceptive activity in the dorsal horn.

57. 2. Supraspinal inhibition
Several supraspinal structures send fibers down the spinal cord to inhibit pain in
the dorsal horn. Important sites of origin for these descending pathways include
the periaqueductal gray, reticular formation, and nucleus raphe magnus (NRM).
Stimulation of the periaqueductal gray area in the midbrain produces widespread
analgesia in humans. Axons from these tracts act presynaptically on primary
afferent neurons and postsynaptically on second-order neurons (or
These pathways mediate their antinociceptive action via α 2 -adrenergic,
serotonergic, and opiate (μ, δ, and κ) receptor mechanisms.
The endogenous opiate system (primarily the NRM and reticular formation) acts
via methionine enkephalin, leucine enkephalin, and β-endorphin.
These opioids act presynaptically to hyperpolarize primary afferent neurons and
inhibit the release of substance P; they also appear to cause some postsynaptic
inhibition.

59. PAIN PERCEPTION
 MRI studies have demonstrated the involvement of the
thalamus & multiple cortical areas in the perception of pain
 How and where the brain perceives pain is still under
investigation.

60. MECHANISM OF REFFERED PAIN
 Referred pain originates at one site (e.g. mandibular first molar) and is
experienced at another site (e.g. the ear).
 When pain is referred to another part of the body, the site of referral is
usually a part of the body that develops from the same embryological
segment or dermatome, as the affected source of the pain.
 Referred pain thus helps in making correct diagnosis of the diseased e.g. Gall
bladder pain is referred to right shoulder tip and cardiac pain to left shoulder
and upper arm.
 The two most popular theories to explain the mechanism of referred pain
are;
 convergence-projection
 convergence-facilitation

61. Convergence-projection theory:
 Most popular theory
 Primary afferent nociceptors from both visceral and
cutaneous neurons often converge onto the same second
order pain transmission neuron in the spinal cord
 The brain, having more awareness of cutaneous than of
visceral structures through past experience, interprets the
pain as coming from the regions subserved by the
cutaneous afferent fibers.

62. visceral afferent nociceptors (S) converge on the same pain-projection neurons as
the afferents from the somatic structures in which the pain is perceived

63. Convergence-facilitation theory
 Similar to the Convergence-projection theory, except that the
nociceptive input from the deeper structures causes the resting
activity of the second order pain transmission neuron in the spinal
cord to increase or be “facilitated”
 The resting activity is normally created by impulse from the
cutaneous afferents.
 “facilitation” from the deeper nociceptive impulses causes the pain
to be perceived in the area that creates the normal, resting
background activity.

64. CONCLUSION
Pain is one of the most common reasons for visiting a physician.
It is estimated that around 40% of adult population may be affected by
chronic pain.
It is estimated that around 40 million people experience musculoskeletal pain
conditions.
Patients with malignant diseases often experience increasing pain as the
disease progresses.
The costs to society related to chronic pain, including costs for procedures to
treat pain are immense.
A proper understanding of pain and its related entities is therefore vital.

65. REFERENCES
1. Morgan & Mikhail’s Clinical Anaesthesiology
2. Miller’s Anaesthesia
3. Guyton And Hall’s Text book of physiology.
4. Internet References

66. Thank you