The document provides an overview of pain pathways and physiology. It discusses: - The anatomy of pain pathways in the nervous system and spinal cord. - The types of nerve fibers (A-delta and C fibers) that transmit pain signals and their characteristics. - The process of pain perception, transmission, and modulation within the nervous system. - Different types of pain (nociceptive, neuropathic, acute, chronic) and clinical pain syndromes. - The gate control theory of pain modulation in the dorsal horn of the spinal cord. - The roles of various opioid receptors (mu, kappa, delta) in mediating analgesia and side effects.

1. Presented by- Dr Neha kumari
First Year MD Student
Moderator- Dr Mumtaz Hussain
Associate Professor,
Dept Of Anesthesiology And Critical Care
IGIMS, Patna

2. Objectives
 Introduction
 Pain-pathway anatomy
 Physiology of pain
-Pain pathway
-Types of pain
-Nerve fibers
-Gateway system
 Clinical implication

3. Pain
 International Association for study of Pain(IASP)-
Unpleasant sensory and emotional experience
associated with actual or potential tissue damage or
described in terms of such damage.
 Pain is redefined as a perception instead of a
sensation because it is a psychological state.
 Latin word "peona " meaning punishment
• Pain is always subjective
• It is differently experienced by each individual.

4. Anatomy of Pain-Pathway
Nervous system & pain-
Somatosensory system has 3-components-
1.Brain-Somatosensory cortex,Thalamus
2.Spinal cord-Dorsal & ventral root
3.PNS-Afferent & Efferent neurons,
A-delta fibre,C fibre
Spinal cord has following parts-
 Gray matter
 White matter
 Gray commissure
 Central canal
 Dorsal & Ventral nerve root

5. -Three major pathway carry information-
 Posterior column
 Anterolateral
Pathway
(Spinothalamic)
 Spinocerebellar
pathway

6. Pain pathway
 Perception of pain
 Transduction of pain
Signal formation-chemical signal- inflammatory
mediators
Electrical activity-Recognises by neurons
 Transmission-transmitted through PNS
A-delta-Fast,small,myelinated,acute pain
C-fiber-Slow,large,unmyelinated,chronic pain
 Modulation-Signal processing in spinal cord(dorsal horn)
& other endogenous system

7. Pathway
 First-order neurons have their cell bodies in the dorsal horn and synapse
on thermoreceptors & nociceptors in the skin.
 The first-order neurons synapse on second-order neurons in the spinal
cord.
 In the spinal cord, the second-order neurons “decussate” cross the line
and ascend to the contralateral thalamus (ventral posterolateral nucleus).
 Decussation usually occurs 1-2 spinal nerve segments above the point of
entry.
 In the thalamus, second-order neurons synapse on third-order neurons,
which ascend to the somatosensory cortex and synapse on fourth-order
neurons.

9. 8/12/2022

10. Anterolateral system
Spinothalamic tract (lateral and
anterior): destined for
thalamus; important in the
localization of painful or
thermal stimuli.
Spinoreticular tract: destined for
reticular formation;
causes alertness and arousal in
response to painful stimuli.
Spinotectal tract: destined for
tectum; orients the eyes
and head towards the stimuli.

11. Cortical pain processing
 Sensory aspects of pain seem to be processed in
somatosensory area
 Emotional distress(Empathy) associated with pain seem to
be processed in Anterior Cingulate Cortex(ACC)

12. Subsystem
 Direct-Direct conscious appreciation of pain
 Indirect-Affective or arousal impact of pain via-
-Spino-reticular-thalamic-cortical pathway -
Spino-mesencephalic pathway(affective impact of
pain)

13. Types of pain
1.Somatic pain-It is a nociceptive pain that arises from
skin,tissue,muscle,bone.
Superficial-skin & subcutaneous
tissue,eg-cuts,burns
deep-muscle,bone,periosteum,fascia
eg-fracture,arthritis,muscle belly rupture
2.Visceral-It is another type of nociceptive pain that
arises from internal organ, eg.Angina pectoris
renal colic,intestinal colic

14. Pain
 Nociceptive pain-Tissue damage
 Neuropathic pain-Nerve damage
 Acute pain-It typically comes on suddenly and has a limited
duration
eg-Damage of tissue such as bone,muscle,organ
 Chronic pain-Lasts longer than acute pain & is
generally resistant to medical T/t
eg-Osteoarthritis,Fibromyalgia
 Breakthrough pain-often happens in between regular
interval

15. pain
 Fast pain-is carried on A-delta,group ΙΙ & ΙΙΙ fibers,has rapid
onset & offset and is precisely located.eg-pin-prick
 Slowpain-is carried on C-fibers & is characterized as
aching,burning or throbbing pain that is poorly localized.eg-
Burn
 Referred pain-is of visceral origin
According to the dermatomal rule –Sites on the skin are
innervated by nerves arising from the same spinal cord segment
as those innervating the visceral organs
Eg-Ischemic heart pain reffered to chest & shoulder
Gallbladder pain is referred to abdomen
Kidney pain is referred to lower back

16. Clinical types of pain
 Somatic
 Visceral
 Referred pain
 Projected pain
 Radiating Pain
 Hyperalgesia
 Allodynia

17. Pain
 Adaptive-Normal response-Tissue damage
Protects from further injury,Inflammation is a large
component
 Maladaptive-Abnormal response
Stimulus is gone but pain persists.eg-inappropriate
managed adaptive pain
 Allodynia-Not typically painful
 Hyperalgesia-Exaggerated response
 Hyperesthesia-Increase loss of sensation

18. Pain - Receptors
 Specialized naked nerve endings found in almost every tissue
of the body.
 Activated by stimuli (mechanical, thermal, chemical)
 Distinguished from other receptors by
 their higher threshold, and
 they are normally activated only by stimuli of noxious
intensity-sufficient to cause some degree of tissue damage.
 Aδ: Myelinated
 C: Unmyelinated

19. Characteristic features of
Aδ & C fibres
Feature Aδ fibre C fibre
Number Less More
Myelination Myelinated Unmyelinated
Diameter 2-5 µm 0.4-1.2 µm
Conduction
velocity
12-30 m/s 0.5 -2 m/s
Specific
stimulus
Most sensitive to
pressure
Most sensitive
for chemical
agents
Impulse
conduction
Fast component of
pain
Slow component
of pain

22. Nociception
 Coined by Sherrington
 Latin: noxa means injury
 it means the ´perception of noxious stimuli
 Pain is termed nociceptive and nociceptive means
sensitive to noxious stimuli
-Noxious stimuli are stimuli that elicit tissue damage and
activates nociceptors
-Nociceptors are free(bare) nerve ending,found in the
skin,muscle,joints,bone & viscera
-A nociceptor is a type of receptor at the end of a sensory
neuron´s axon that responds to damaging or
Potentially damaging stimuli by sending possible threat signals
to the spinal cord and brain

24. Location of nociceptors
Pain detecting
receptors,found through out
the body-
 Superficial skin layers
 Deeper tissues
 Periosteum, joints, arterial
wall, liver capsule, pleura
 Other deeper tissues
 Sparse pain nerve endings
 But wide spread tissue
damage results in pain

25. Types of Nociceptors
 Somatic
 Free nerve endings of Aδ & C fibres
 Visceral
 Wide spread inflammation, ischemia, mesentric
streching , spasm or dilation of hollow viscera produces
pain
 Probably strech receptors

26. Pain stimuli
 Mechanical / thermal stimuli
 Fast pain: Sharp well localized , pricking type
 Chemical stimuli
 Slow pain: poorly localized, dull, throbbing
 Bradykinin, histamine
 Serotonin, Prostaglandins
 Substance P

27. Neurochemicals of pain
 Pain initiators-
central-Glutamate,Substance P
Peripheral-Bradykinin,Prostaglandins
 Pain inhibitors-
Serotonin,Endorphin,enkephalin,
Dynorphin

28. Supra
spinal
pain
supression
system

29. Gate control system
 Gate control theory of pain was proposed by Ronald
Melzack and Patrick Wall in 1965
 According to this theory, painful information is
projected to the supraspinal brain regions if the gate is
open, whereas painful stimulus is not felt if the gate is
closed by the simultaneous inhibitory impulses.

30.  Usually, rubbing the skin of painful area seems to somehow
relieve the pain associated with a bumped elbow.
 In this case, rubbing the skin activates large-diameter
myelinated afferents (A beta), which are “faster” than A
delta fibers or C fibers conveying painful information.
 These A-beta fibers deliver information about pressure and
touch to the dorsal horn and override some of the pain
messages (“closes the gate”) carried by the A-delta and
C fibers by activating the inhibitory interneurons in the
dorsal horn
 This hypothesis provided a practical theoretical basis for
some approaches such as massage, transcutaneous nerve
stimulation, and acupuncture to treat pain in patients.

31. Gate control system

32. Physiological effect of pain
 CVS-Increases HR,BP,PVR
 MI,Dysrhythmias
 GIS-Impaired gastrointestinal function-delayed gastric emptying &
reduced bowel motility,anastomotic failure
 Respiratory system-Respiratory dysfunction.atelectasis,Pneumonia
 Genitourinary system-Increases release of hormones & enzymes
 Musculoskeletal system-Reflex muscle spasm,venous stasis,increases
coagulability
 Immune system-Depression
 Hypercoagulable state-DVT,PE
 Psychological & cognitive effects-anxiety,depression,fatigue
 Nausea,Vomitting
 Chronic pain

33. Pain assessment tool
 For young infant-1.PIPP-Premature Infant Pain Profile
1.three behavioural-facial action-brow buldge,eye
squeez & nasolabial furrow and two physiological
heart rate,oxygen saturation
2.FLACC SCORE
 3-7 yrs old child-FACES scale,CHEOPS scale
 Children>8yrs-VAS score ,numerical rating scale

36. Opioid Receptors
Found in the brain, spinal cord and
peripheral nervous system as:
Mu (μ)
Kappa (k)
Delta (δ)
Nociceptin/Orphanin (N/OFQ)

37. RECEPTOR ENDOGENOUS LIGAND EFFECT ON RECEPTOR
STIMULATION
Mu(μ) Endorrphin Supraspinal analgesia
(μ1)
Dependance (μ2)
Respiratory depression
(μ2)
Constipation (μ2) ,
miosis (μ2)
Kappa(ĸ) Dynorphin Spinal analgesia
Sedation
Miosis
Delta(δ) Enkephalins Respiratory depression
Sigma(σ) Unknown Dysphoria
OPIOID RECEPTORS, THEIR ENDOGENOUS
LIGANDS AND EFFECT PRODUCED ON
RECEPTOR STIMULATION

38. μ -Receptor
μ1
 Located outside
spinal cord
 Higher affinity for
morphine
 Supraspinal
analgesia
 Selectively blocked
by naloxone
μ2
 Located throughout
CNS
 Responsible for
 spinal analgesia,
 Respiratory
depression,
 constipation
 physical dependence,
and euphoria

39. Kappa Receptor
 Only modest analgesia(spinal κ1 and supraspinal
κ3)
 Little or no respiratory depression
 Little or no dependence
 Dysphoric effects
 Miosis
 Reduced GI motility

40. Delta Receptor
 High affinity for enkephalins endogenous ligands.
 The δ mediated analgesia is mainly spinal
 Affective component of supraspinal analgesia
appears to involve δ receptors as these receptors
are present in limbic areas—also responsible for
dependence and reinforcing actions.
 The proconvulsant action is more prominent in δ
agonists.