2. A GLIMPSE…
• IASP definition of pain
• Pain receptors
• Fast pain and the slow pain
• Pain pathway
• Pain processing
• Various theories of pain
• Referred pain and visceral pain
• Neuropathic pain and mechanism
• CRPS (Complex regional pain syndrome)
• Pain and the Surgical stress response
• Preventive analgesia
3. The word pain is derived from the Latin word Peone and the Greek word
Poine meaning penalty or punishment
Definition of pain
(proposed by the 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.”
Pain is SUBJECTIVE phenomena
4. • The definition of pain as proposed by the International Association for the Study
of Pain emphasizes the complex nature of pain as a physical, emotional, and
psychological condition.
• Failure to appreciate the complex factors that affect the experience of pain and
relying entirely on physical examination findings and laboratory tests may lead to
misunderstanding and inadequate treatment of pain
5. PAIN RECEPTORS AND
THEIR STIMULATION
• Nociceptors are free nerve endings located in skin, muscle, bone, 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 and connective tissue
with cell bodies located in the dorsal root ganglia
Non-adapting Nature of Pain Receptors.
• In contrast to most other sensory receptors of the body, pain receptors adapt
very little and sometimes not at all
6. SKIN RECEPTORS FOR PAIN
HIGH THRESHOLD
MECHANORECEPTORS
( HTMS)
POLYMODAL RECEPTORS
These receptors detect
local deformation
Eg: Touch
These receptors detect a
variety of stimuli causing
injury
Eg: Heat
Noxious stimulation
These do not have a
specialized and simple
nerve endings in the
periphery
7. Fast pain and the Slow pain
(based on transmission)
• Pain has been classified into two major types: fast pain and slow pain. Fast pain is
felt within about 0.1 second after a pain stimulus is applied, whereas slow pain
begins only after 1 second or more and then increases slowly over many seconds
and sometimes even minutes
8. Fast pain and the Slow pain
(based on transmission)
• Pain has been classified into two major types: fast pain and slow pain. Fast pain is
felt within about 0.1 second after a pain stimulus is applied, whereas slow pain
begins only after 1 second or more and then increases slowly over many seconds
and sometimes even minutes
• Fast pain also known as first pain is also described by many alternative names,
such as sharp pain, pricking pain, acute pain, and electric pain. This type of pain is
felt when a needle is stuck into the skin, when the skin is cut with a knife, or
when the skin is acutely burned. It is also felt when the skin is subjected to
electric shock. Fast-sharp pain is not felt in most deep tissues of the body.
9. Fast pain and the Slow pain
(based on transmission)
• Pain has been classified into two major types: fast pain and slow pain. Fast pain is felt
within about 0.1 second after a pain stimulus is applied, whereas slow pain begins only
after 1 second or more and then increases slowly over many seconds and sometimes
even minutes
• Fast pain also known as first pain is also described by many alternative names, such as
sharp pain, pricking pain, acute pain, and electric pain. This type of pain is felt when a
needle is stuck into the skin, when the skin is cut with a knife, or when the skin is acutely
burned. It is also felt when the skin is subjected to electric shock. Fast-sharp pain is not
felt in most deep tissues of the body.
• 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
10. NERVE FIBRES INVOLVED IN PAIN TRANSMISSION
A FIBRES C FIBRES
A – BETA
FIBRES
A – DELTA FIBRES
Large Thick Myelinated (12-20
microns)
Fast conducting, velocity 40-70
m/s
Low threshold mechano
Receptors
Specialized nerve endings called
“Pacinian corpuscles”
Small (1-4microns) Lightly
Myelinated
Slowconducting, velocity 10-
35 m/s
Respond to high threshold
mechano&thermal Receptors
sharp sensation of pain
Small & unmyelinated(0.5 – 1.5
microns)
Very slow conducting, velocity
0.5- 2 m/s
Stimulated mostly by chemical
stimuli but Respond to all types
of noxious stimuli
Require high intensity stimuli to
trigger a response
11. Pain Pathway
• The nociceptive pathway is an afferent
three-neuron dual ascending (e.g.,
anterolateral and dorsal column medial
lemniscal pathways) system, with
descending modulation from the cortex,
thalamus, and brainstem
12. Pain Pathway
The first order neurons:
• The first-order neurons that make up the
dual ascending system have their origins in
the periphery as A delta and polymodal C
fibers. First-order neurons synapse on
second-order neurons in the dorsal horn
primarily within laminas I, II, and V, where
they release excitatory amino acids and
neuropeptides
13. • Some fibers can ascend or
descend in Lissauer’s tract
prior to terminating on
neurons that project to
higher centers.
LISSAUER’TRACT:
• Tip of the posterior column
near posterior nerve roots
14. • Second-order neurons consist of
nociceptive-specific and wide dynamic-
range (WDR) neurons.
• Nociceptive-specific neurons are located
primarily in lamina I, respond only to
noxious stimuli, and are thought to be
involved in the sensory-discriminative
aspects of pain.
• WDR neurons are predominately located
in laminae IV, V, and VI, respond to both
non-noxious and noxious input, and are
involved with the affective motivational
component of pain
15. Spinal Cord Internal Structure
Lamina of Rexed
Lamina I ---------- marginal layer
Lamina II ------- substantia gelatinosa
of Rolando
Lamina III, IV ----- nucleus proprius
16. Spinal Cord Internal Structure
Lamina of Rexed
Lamina V: Neck of the doral horn. Neurons
Within Lamina V are mainly involved in processing
Sensory afferent stimuli from cutaneous,
Muscle and joint mechano receptors
Lamina VI: Base of the doral horn,
Fast pain moves to Lamina VI, which controls
Withdrawl reflex
17. Spinal Cord Internal Structure
Lamina of Rexed
VII to X intermediate zone
Lamina VII --------- intermediate gray
intermedio-lateral cell column (IML)
Clarke’s column (Nucleus dorsalis)
intermedio-medial cell column (IMM)
Lamina VIII----------motor interneurons
Lamina IX ----------
Lateral and medial motor neurons at limb regions
phrenic/ spinal accessory nuclei at cervical
Onuf’s nucleus in the sacral region
Lamina X ----------- gray commissure, grey matter surrounding the central canal
18. • Axons of both nociceptive-specific
and WDR neurons ascend the spinal
cord via the dorsal column- medial
lemniscus and the anterior lateral
spinothalamic tract to synapse on
third-order neurons in the
contralateral thalamus, which then
project to the somatosensory cortex
where nociceptive input is perceived
as pain
19. Pain Processing
• hyperalgesia, is defined as an
exaggerated pain response to a
normally painful stimulus, and
allodynia, is defined as a
painful response to a typically
non-painful stimulus
• The four elements of pain
processing include (1)
transduction, (2) transmission,
(3) modulation, and (4)
perception
20. • Transduction is the event whereby noxious thermal, chemical, or mechanical
stimuli are converted into an action potential.
• Transmission occurs when the action potential is conducted through the
nervous system via the first-, second-, and third-order neurons, which have cell
bodies located in the dorsal root ganglion, dorsal horn, and thalamus,
respectively
• Modulation of pain transmission involves altering afferent neural transmission
along the pain pathway. The dorsal horn of the spinal cord is the most common
site for modulation of the pain pathway, and modulation can involve either
inhibition or augmentation of the pain signals.
21. • Examples of inhibitory spinal
modulation include (1) release of
inhibitory neurotransmitters such
as gamma-amino butyric acid
(GABA) and glycine by intrinsic
spinal neurons, and (2) activation
of descending efferent neuronal
pathways from the motor cortex,
hypothalamus, periaqueductal gray
matter, and the nucleus raphe
magnus, which results in the
release of norepinephrine,
serotonin, and endorphins in the
dorsal horn
22. • Spinal modulation, which
results in augmentation of
pain pathways, is manifested
as central sensitization, which
is a consequence of neuronal
plasticity. The phenomenon
of “wind-up” is a specific
example of central plasticity
that results from repetitive C-
fibre stimulation of WDR
neurons in the dorsal horn.
23. • Perception of pain is the
final common pathway, which
results from the integration
of painful input into the
somatosensory and limbic
cortices.
• Generally speaking,
traditional analgesic
therapies have only targeted
pain perception. A
multimodal approach to pain
therapy should target all four
elements of the pain
processing pathway
24. CHEMICAL MEDIATORS OF
TRANSDUCTION AND TRANSMISSION
• Tissue damage following surgical
procedures leads to the activation of
small nociceptive nerve endings and local
inflammatory cells (e.g., macrophages,
mast cells, lymphocytes, and platelets) in
the periphery.
• Antidromic release of substance P and
glutamate from small nociceptive
afferents results in vasodilation,
extravasation of plasma proteins, and
stimulation of inflammatory cells to
release numerous algogenic substances
26. CHEMICAL MEDIATORS OF
TRANSDUCTION AND TRANSMISSION
• This chemical milieu will both directly
produce pain transduction via
nociceptor stimulation as well as
facilitate pain transduction by
increasing the excitability of
nociceptors. Peripheral sensitization
of polymodal C fibers and high-
threshold mechanoreceptors by
these chemicals leads to primary
hyperalgesia, which by definition is
an exaggerated response to pain at
the site of injury
27. CHEMICAL MEDIATORS OF
TRANSDUCTION AND TRANSMISSION
• the dorsal horn of the spinal cord contains numerous transmitters and receptors involved in pain
processing. Three classes of transmitter compounds integral to pain transmission include
(1) the excitatory amino acids glutamate and aspartate,
(2) the excitatory neuropeptides substance-P and neurokinin A, and
(3) the inhibitory amino acids glycine and GABA.
The various pain receptors include (1) the NMDA (N-methyl-d-aspartate), (2) the AMPA (alpha-
amino-3-hydroxy-5-methylisoxazole-4-proprionic acid), (3) the kainate, and (4) the metabotropic
28. CHEMICAL MEDIATORS OF
TRANSDUCTION AND TRANSMISSION
• The AMPA and kainate receptors, which are
sodium channel dependent, are essential for fast
synaptic afferent input.
29. CHEMICAL MEDIATORS OF
TRANSDUCTION AND TRANSMISSION
• The AMPA and kainate receptors, which are
sodium channel dependent, are essential for fast
synaptic afferent input.
• On the other hand, the NMDA receptor, which is
calcium channel dependent, is only activated
following prolonged depolarization of the cell
membrane. Release of substance P into the
spinal cord will remove the magnesium block on
the channel of the NMDA receptor giving
glutamate free access to the NMDA receptor.
30. CHEMICAL MEDIATORS OF
TRANSDUCTION AND TRANSMISSION
• The AMPA and kainate receptors, which are sodium
channel dependent, are essential for fast synaptic
afferent input.
• On the other hand, the NMDA receptor, which is
calcium channel dependent, is only activated
following prolonged depolarization of the cell
membrane. Release of substance P into the spinal
cord will remove the magnesium block on the
channel of the NMDA receptor giving glutamate
free access to the NMDA receptor.
• Repetitive C-fiber stimulation of WDR neurons in
the dorsal horn at intervals of 0.5 to 1 Hz can
precipitate the occurrence of wind-up and central
sensitization. This leads to secondary hyperalgesia,
which, by definition, is an increased pain response
evoked by stimuli outside the area of injury
31. VARIOUS PAIN THEORIES
Pain theories are proposed to offer the possible physiologic mechanisms
involved in pain. They are as follows
Specificity theory
Pattern theory
Neuromatrix theory
Gate control theory
SPECIFICITY THEORY: This theory states pain as separate modality evoked by
specific receptors that transmit information to pain centres or regions in the
forebrain where pain is experienced.
32. PATTERN THEORY
• Pain receptors share endings or pathways with other sensory modalities
but different patterns of activity of the same neurons can be used to signal
painful and non – painful stimuli
•Eg. Light touch applied to skin would produce the sensation of touch and
intense pain pressure would produce pain through high frequency firing of
the same receptor
NEUROMATRIX THEORY
This theory was put forward by MELZACK
This theory explains the role of brain in pain as well as the multiple
dimensions and determinants of pain
33. According to this theory the brain contains a widely distributed neural
network called the body self Neuromatrix that contains somatosensory,
limbic, & Thalamocortical components
The body self Neuromatrix involves multiple input sources such as
Somatosensory inputs
Other impulses/ inputs affecting the interpretation of the
situation
Various components of stress regulation systems
Intrinsic neural inhibitory modulatory circuits
34. GATE CONTROL MECHANISM
Proposed by MELZACK & WALL IN 1965
According to this theory, the pain stimuli transmitted by afferent pain fibres are
blocked by GATE MECHANISM located at the posterior gray horn of the spinal
cord
The gate control theory of pain asserts that non-painful input closes the
"gates" to painful input, which prevents pain sensation from traveling to the
central nervous system. Therefore, stimulation by non-noxious input is able to
suppress pain.
If the gate is open pain is felt, and if the gate is closed pain is suppressed
Impulses in A – δ & C – fibres can be blocked by modulated A – β activity that can
selectively block impulses from being transmitted to the transmission cells in the
spinal cord and then to CNS resulting in no pain
35. ROLE OF BRAIN IN GATE CONTROL MECHANISM
Gates in spinal cord are open
Pain signals reach the thalamus through lateral spinothalamic tract
Signals are processed in thalamus
Signal are sent to sensory cortex & perception of pain occurs in
cortex
Signals are sent from cortex back to spinal cord and the gate is
closed by releasing pain relievers such as opioid peptides
Minimizing the severity & extent of pain
36.
37. Applications of gate theory
Stimulation of touch fibres for pain relief:
• TENS (transcutaneous electrical nerve stimulation)
• Acupuncture
• Massage
38. REFERRED PAIN & VISCERAL PAIN
• Often a person feels pain in a part of the body that is fairly remote from the tissue causing the
pain. This phenomenon is called referred pain.
• For instance, pain in one of the visceral organs often is referred to an area on the body surface.
Knowledge of the different types of referred pain is important in clinical diagnosis because in
many visceral ailments the only clinical sign is referred pain
39. Mechanism of Referred Pain.
• branches of visceral pain fibers are
shown to synapse in the spinal cord
on the same second-order neurons
(1 and 2) that receive pain signals
from the skin. When the visceral pain
fibers are stimulated, pain signals
from the viscera are conducted
through at least some of the same
neurons that conduct pain signals
from the skin, and the person has
the feeling that the sensations
originate in the skin.
40. VISCERAL PAIN
• visceral pain differs from surface pain in several important aspects. One of the most important
differences between surface pain and visceral pain is that highly localized types of damage to the
viscera seldom cause severe pain
• Conversely, any stimulus that causes diffuse stimulation of pain nerve endings throughout a viscus
causes pain that can be severe. For instance, ischemia caused by occluding the blood supply to a
large area of gut stimulates many diffuse pain fibers at the same time and can result in extreme
pain.
Causes of True Visceral Pain
• chemical damage to the surfaces of the viscera, spasm of the smooth muscle of a hollow viscus,
excess distention of a hollow viscus, and stretching of the connective tissue surrounding or within
the viscus.
• Essentially all visceral pain that originates in the thoracic and abdominal cavities is transmitted
through small type C pain fibers and, therefore, can transmit only the chronic-aching-suffering
type of pain.
41. OTHER CAUSES OF VISCERAL PAIN INCLUDE:
• Ischemia
• Chemical stimuli
• Spasm of a hollow viscus
• Over distension of a hollow viscus
Localization of Referred Pain Transmitted via Visceral Pathways:
• For instance, the heart originated in the neck and upper thorax, so the heart’s visceral
pain fibers pass upward along the sympathetic sensory nerves and enter the spinal cord
between segments C3 and T5. Therefore pain from the heart is referred to the side of the
neck, over the shoulder, over the pectoral muscles, down the arm, and into the substernal
area of the upper chest.
42. Referred Pain From the Viscera
• The stomach originated
approximately from the seventh to
ninth thoracic segments of the
embryo. Therefore, stomach pain is
referred to the anterior epigastrium
above the umbilicus, which is the
surface area of the body subserved by
the seventh through ninth thoracic
segments.
43. Parietal Pathway for Transmission of Abdominal and Thoracic Pain
• Pain from the viscera is frequently localized to two
surface areas of the body at the same time because
of the dual transmission of pain through the referred
visceral pathway and the direct parietal pathway
• Pain impulses pass first from the appendix through visceral
pain fibers located within sympathetic nerve bundles, and
then into the spinal cord at about T10 or T11; this pain is
referred to an area around the umbilicus and is of the
aching, cramping type. Pain impulses also often originate in
the parietal peritoneum where the inflamed appendix
touches or is adherent to the abdominal wall. These
impulses cause pain of the sharp type directly over the
irritated peritoneum in the right lower quadrant of the
abdomen
44. NEUROPTHIC PAIN
Neuropathic pain is a result of an injury or malfunction of the nervous
system
It is described as
Aching
Throbbing
Burning
Shooting
Stinging
Tenderness/ sensitivity of skin
45. MECHANISM OF NEUROPATHIC PAIN
Nerve damage/ persistent stimulation
Rewiring of pain circuits both anatomically &
biochemically
Spontaneous nerve
stimulation
Autonomic neuronal
stimulation
Increased discharge of
dorsal horn neurons
NEUROPATHIC PAIN
Results in
causing
Finally leading to
46. Complex regional pain syndrome (CRPS)
are defined as “a variety of painful conditions following injury, which appears regionally having a
distal predominance of abnormal findings, exceeding in both magnitude and duration the expected
clinical course of the inciting event often resulting in significant impairment of motor function, and
showing variable progression over time.”
1. Two forms of CRPS are type I (reflex sympathetic dystrophy, absence of major nerve injury) and
type II (causalgia, presence of a major identifiable nerve injury).
2. The incidence of CRPS I is 1% to 2% after fractures, 12% after brain lesions, and 5% after
myocardial infarction, and the incidence of CRPS II in peripheral nerve injury varies from 2% to 14%
47. 3. The mechanism underlying the pathogenesis of CRPS remains unclear, although
it is recognized that CRPS is a neurologic disease, including the autonomic, sensory,
and motor systems as well as cortical areas involved in the processing of cognitive
and affective information, and the inflammatory component appears to be
particularly important in the acute phase of the disease.
4. Effective, evidence-based treatment regimens for CRPS are lacking.
48. PAIN & THE SURGICAL STRESS RESPONSE
• Although similar, postoperative pain and the surgical stress response are not the same. Surgical
stress causes release of cytokines (e.g., interleukin-1, interleukin-6, and tumor necrosis factor-
alpha and precipitates adverse neuroendocrine and sympatho-adrenal responses, resulting in
detrimental physiologic responses, particularly in high-risk patients
• The increased secretion of the catabolic hormones such as cortisol, glucagon, growth hormone,
and catecholamines and the decreased secretion of the anabolic hormones such as insulin and
testosterone, characterize the neuroendocrine response.
• The end result of this is hyperglycemia and a negative nitrogen balance, the consequences of
which include poor wound healing, muscle wasting, fatigue, and impaired immunocompetency.
The sympatho-adrenal response has detrimental effects on numerous organ systems
50. PREVENTIVE ANALGESIA
• Preventive analgesia includes any anti-nociceptive regimen delivered
at any time during the perioperative period that will attenuate pain
induced sensitization.
• The term “preventive analgesia” replaces the older term “pre-
emptive analgesia”, which is defined as an analgesic regimen that is
administered prior to surgical incision and is more effective at pain
relief than the same regimen administered after surgery.
51. PREVENTIVE ANALGESIA
• In order for preventive analgesia to be successful, three critical principles must be adhered to:
(1) The depth of analgesia must be adequate enough to block all nociceptive input during
surgery,
(2) the analgesic technique must be extensive enough to include the entire surgical field, and
(3) the duration of analgesia must include both the surgical and post surgical periods. Patients
with pre-existing chronic pain may not respond as well to these techniques because of pre-existing
sensitization of the nervous system
