This document provides an overview of the pathophysiology of pain. It discusses the definition of pain, pain receptors and pathways in the peripheral and central nervous systems. It describes the gate control theory of pain modulation in the spinal cord and descending pain inhibitory pathways in the brain. The document also covers physiological and psychological effects of pain, classifications of pain including nociceptive and neuropathic pain, and assessments used to evaluate pain.

1. SEMINAR
PATHOPHYSIOLOGY
OF PAIN

2.  INTRODUCTION
 PATHOPHYSIOLOGY OF PAIN
PERCEPTION
 PHYSIOLOGICAL EFFECTS OF PAIN
 CLASSIFICATION OF PAIN
 ASSESSMENT OF PAIN

3. INTRODUCTION
 Latin word ‘Poena’ - Penalty or punishment.
Definition : IASP - “An unpleasant and emotional experience
associated with actual or potential tissue damage or described in
terms of such damage”.
Sherrington – “The psychical (pertaining to mind) adjunct (joint to)
of an imperative (urgent) protective reflex”.
 Subjective experience.
 Awareness of harmful agent.
 Reflex withdrawal response.
 Pain sensation has a protective function.

4. Why pain should be treated ?
 To releive suffering
 Reflex muscle spasm
• Respiratory embarrassment
• Itself can be major cause of severe pain
 Untreated pain will keep getting worse
 Anatomical and genetic changes

5. PATHOPHYSIOLOGY OF PAIN PERCEPTION
 Two major classes
 Normal or nociceptive
 Abnormal or pathophysiologic
 Nociception : “Complex series of physiologic events that
occurs between the initiation of tissue damage and perception
of pain”
Four processes
• Transduction :
• Transmission :
• Modulation :
• Perception :

6. PAIN RECEPTORS
The receptors which mediate pain is called nociceptors
Nociceptors - Two types of nerve fibers.
a) Aδ myelinated nerve fibers
b) C unmyelinated nerve fibers
Points Aδ Fibre nociceptor C fibre nociceptor
1) Number Less More
2) Myelination Myelinated Unmyelinated
3) Diameter 2 – 5 micron 0.4 – 1.2 micron
4) Conduction
velocity
12 – 30 m/sec 0.5 – 2 m/sec
5) Neurotransmitter Glutamic acid Substance P
7) Impulse
conduction
Noxious stimulus
Fast component
Thermal & mechanical
stimulus, Slow component
9) Sensitivity to
electrical stimulus
More Less

7. Pain receptors are activated by three noxious stimuli
• Mechanical, • Thermal, • Chemical
 Mechanical :
• Excessive pressure or tension on nerve
• E.g. blow on the head, pulling of hair, pain of child birth.
 Thermal :
• Raising skin temperature above 450
C or exposure to cold
(00
) is painful.
 Chemical :
• Endogenous – Histamine, Kinins, prostaglandin released
from damaged tissue.
• Exogenous – H2SO4, HCl, H2O2

8. Chemical mediators of pain acting on nociceptors
 Potassium, ATP, ADP
 Bradykinines
 Leukotrines
 Serotonin
 Histamines
 Prostaglandins
Excitatory Inhibitory
Substance P Somatostatin, acetyl choline
Calcitonine gene related peptides Enkephalins, β-endorphins
Glutamate Norepinephrine, adrenaline
Aspartate GABA
ATP Glycine
Chemical mediators of pain acting on CNS

9. NEURAL PATHWAYS FOR PAIN
Three neuron pathways
1. First order neurons :
 Dorsal root ganglion
2. Second order neurons :
 Spinal cord and arranged as 10 laminae of rexed.
 Cross to the opposite side and form the spino thalamic tract.
 Two types of nociceptive spinal projection of second order
neurons are
• Wide dynamic range – Aδ, C, Aβ fibers
Both noxious
Non noxious stimulus.
• Neuron specific - Aδ, C fibers
Noxious stimulus.
3. Third order neurons :
 Thalamus  somato sensory area i.e I & II.

10. PATHWAYS FOR THE FAST PAIN
In peripheral nerves :
 Aδ
 velocities between 6 and 30
m/sec
 DRG  spinal cord
In the spinal cord :
 Tract of Lissauer
 Lamina I.
 Opposite side
 Neospinothalamic tract.
In the brain stem : Reticular
formation  thalamus.
In the thalamus : Ventral
posterolateral nucleus 
Primary sensory cortex.

11. PATHWAYS FOR SLOW PAIN
In peripheral nerves :
 Unmyelinated C fibres
 Velocities ranging from 0.5 to 2
m/sec
 DRG  Spinal cord
In the spinal cord :
 Laminae II and III
 Substantia gelatinosa
 Crosses the midline
 Paleospinothalamic tract
In the brain stem :
 Reticular formation, and also in
superior colliculus, and
periaqueductal grey region.
 Intralaminar nuclei and posterior
nuclei of thalamus
 Hypothalamus
 Brain

12. PAIN SUPPRESSION SYSTEMS IN CNS
Two major components:
 Spinal pain suppression system, and
 Supraspinal pain suppression system.
Spinal pain suppression system
Gate control hypothesis
 Metzak and Wall in 1965.
 Dorsal grey horn
• Segmental suppression
• Supraspinal suppression

13. A. Segmental Suppression :
 Myelinated (Aβ) touch fibres
 Collateral
 Presynaptic inhibition
 Blocking calcium channels
Clinical application
 Local application of warmth and cold
 Rubbing or massage or pressure in the vicinity of painful area
 Local application of counter irritants
 Acupuncture
 Transcutaneous electric nerve stimulation

14. Supraspinal pain suppression system :
 Descending serotonergic and opiod inhibitory
system
 Descending purinergic inhibitory system and
 Descending adrenergic inhibitory system

15. Descending serotonergic and
opioid inhibitory system :
Components
 Raphe Magnus Nucleus (RMN) :
 Lower pons and upper
medulla.
 Periaqueductal Grey (PAG)
reticular formation,
hypothalamus, and frontal
cortex.
 Serotonin and substance P.
 Project down the dorsolateral
column
 postsynaptic inhibition.

16.  Periaqueductal grey (PAG) area
in the midbrain
 Raphe Magnus Nucleus
(RMN)
 Opioid receptors
 Four types of opioid
receptors µ,κ,δ and σ.
 Stimulation
 Pain suppression circuitry
 Reduced pain perception.

17.  Primary afferent pain
carrying fibres
 Substantia gelatinosa of
dorsal horn.
 Substance P as
neurotransmitter.
 endorphin and enkephalin
 Decrease the release of
substance P
 Presynaptic inhibition.
 Stimulate both i.e. PAG
as well as RMN.
 OPIOID RECEPTORS
 Hypothalamus and frontal cortex
 Stimulate – PAG as well as RMN

18. Descending purinergic inhibitory system :
 Adenosine.
 Pre and postsynaptic
 Excitatory amino acid release.
Descending noradrenergic inhibitory system :
 Locus coeruleus and medullary reticular formation
 Dorsolateral fasciculus.
 Stress
Pain perception in children –
 26th
week of gestation
 It has larger receptor field
 High concentration of receptors sites for substance P
 Less developed descending inhibitory pathway.

19. PHYSIOLOGICAL AND PSYCHOLOGICAL EFFECTS OF PAIN
Respiratory system
 Reduction in lung volume (TV, VC, FRC)
 Regional lung collapse (atelectasis)
 Decrease alveolar ventilation leads to hypoxemia and hyper
capnia.
 Cough is decreased
 Secretions are retained
 Chances of chest infections are more
 Increase O2 consumption
 Increase metabolic substrate formation.

20. Cardiovascular system :
 Increase in HR, BP, CO, Systemic and coronary vascular
resistance.
 Increase in cardiac work and myocardial oxygen consumption
 Decrease myocardial oxygen delivery
 Risk of ischaemia, infarction and deep venous thrombosis
increases.
Gastrointestinal and genitourinary system :
 Increases intestinal secretion
 Increases smooth muscle sphincter tone
 Decreases gastrointestinal motility (stasis & ileus)
 Increase bladder sphincter tone – retention of urine.

21. Neuroendocrine and metabolic effects :
 ↑ Catabolic hormones e.g. ACTH, ADH, GH, Cortisol,
Catecholamines, renin, angiotensin II, aldosteron, glucagon.
 ↓ Anabolic hormones e.g. insulin and testosterone.
 Ebb phase Flow phase Catabolism.
 Net resulting negative nitrogen balance.
Carbohydrates metabolism :
 Hyperglycemia, glucose intolerance, insulin resistance.
Protein metabolism :
 Muscle protein catabolism
Fat metabolism :
 Increase lypolysis and oxidation

22. Immunological :
 Immune dysfunction.
 Infection
 Tumour recurrence
Coagulations :
 Deep venous thrombosis and pulmonary embolism
PSYCHOLOGICAL RESPONSE :
Behaviour :
 Self absorption and concern, withdrawal from inter personal
contact, increase sensitivity to external stimuli, grimacing,
postering, reduced activity and seeking help and attention.
Affect :
 Fear and anxiety
 Feeling of helplessness, loss of control, depression and
insomnia.

23. CLASSIFICATION OF PAIN
A) Physiological pain
 Brief noxious stimulus
 Activates receptors
 Impulse modification
 Normal neural processing
 Allerting mechanism
 Good correlation
B) Clinical pain
 Prolonged noxious stimulus
 Activates receptors
 Peripheral and central sensitization
 Two types – Nociceptive and Neuropathic

24. I) Nociceptive pain –
 Stimulation of nociceptor.
 Primary and secondary hyperalgesia and allodynia.
 Hyperalgesia – An increased response to a stimulus which is
normally painful.
• Primary hyperalgesia – excessive sensitivity of pain
receptors itself e.g. sunburned skin.
• Secondary hyperalgesia – means facilitation of sensory
transmission.
 Allodynia – Pain due to a stimulus which does not normally
provoke pain.
 Protective function
 Poor correlation

25. II) Neuropathic pain –
“Pain associated with injury, disease or surgical section of the
peripheral and central nervous system”
 Three types :
 Neural injury pain – e.g.
 Nerve compression pain – e.g.
 Complex regional pain syndrome
 CRPS – I : Reflex symphathetic dystrophy – “Continuous
pain in a portion of extremity after trauma which may
include fracture but not involved major nerve, associated
with symphathetic over activity”
 CRPS – II : Causalgia – “Burning pain, allodynia, usually in
the hand and foot after partial injury of a nerve or one of its
major branches”
 No correlation between injury and pain perception

26. Acute pain Chronic pain
1) Pain of recent onset and
limited duration with identifiable
relation with injury of disease
1) Pain which persist a month beyond the
usual course of an acute disease or a
reasonable time for an injury to heal
3) Usually caused by noxious
stimulation
3) Cause is often unclear. Psychological
and environmental factors play major role
5) Disappear with t/t of cause 5) Often unresponsive to many form of
treatment
6) Opioids typically effective and
indicated
6) Poorly effective
7) Most commonly – acute
medical illness, MI, pancrititis,
renal colic
7) Commonly in chronic backache and
cancer pain.
CLASSIFICATION ACCORDING TO DURATION OF PAIN

27. Fast Pain
 Aδ fibers
 Sharp, well localized and pricking sensation
 Within 0.1 msec
 Accompanient of fast pain
• Reflex withdrawal response
• Sympathetic response i.e. increase BP, HR,
respiration.
 Not radiate.

28. Slow pain :
 C fibres
 Poorly localised, dull, throbbing, burning sensation
 After 1 sec
 Accompanient
• Unpleasantness, irritation, frustration and depression.
• Nausea, vomiting, sweating, bradycardia, hypotension.
• Generalized reduction of skeletal muscle tone

29. CLINICAL TYPES OF PAIN
 Somatic pain and visceral pain
 Referred pain and radiating pain
Somatic pain :
 Arises from the tissue of the body other than the viscera.
a) Superficial somatic pain
• Skin and subcutaneous tissue.
• Similar to the fast pain.
a) Deep somatic pain
• Muscle, joints, bones and fascia.
• Similar to slow pain.
 Clinical condition
• Injuries
• Tissue ischaemia
• Inflammation of tissues
• Muscle spasm

30. Visceral pain :
 Poorly localized
 Unpleasant
 Nausea, vomiting, decrease BP & HR profuse sweating.
 GUARDING
 Radiates or referred to other site
 C fibres.
Common causes :
 Inflammation of viscera
 Over distension of hollow viscus.
 Spasm of hollow viscus.
 Chemical stimuli
 Ischaemia

31. Referred pain :
 Pain which originates due to irritation of visceral organ and
is felt not in the organ but in some another somatic
structure. (skin) supplied by same neural segment.
 DERMATOMAL RULE.
e.g.
 Myocardial infarction
 Stone in ureter
 Inflammation of diaphragm

32. THEORIES OF REFERRED PAIN
 Convergence theory
 Facilitation theory
Convergence theory :
 First order neuron
 Somatic area and a visceral organ
 Second order neuron
 Source of pain
 Somatic pain is more common
Facilitation theory :
 The visceral irritation
 Facilitates pain fiber
 Even minor somatic irritation
 Pain
Radiating pain :
• Pain seems to spread from local area to the distant site is
called radiating pain.
• E.g. in appendicitis, pain starts in right iliac fossa and
radiates towards centre of abdomen.

33. ASSESSMENT OF PAIN
Evaluation of pain in children and adults
 Verbal rating scale
 0 – No pain
 1 – Mild pain
 2 – Moderate pain
 3 – Severe pain
 Verbal Numerical rating scale
 0 – 10
 0 – No pain
 10 – Worst pain
 Visual analog scale
 10 cm horizontal line
 No pain at one end
 Worst possible pain on other end
 Describe intensity not the quality

34.  McGill’s pain questionnaire
 20 aspects
 1 – 10 – Sensory aspects
 11 – 15 – Affective aspects
 16 – evaluative aspects or
 17 – 20 – Other miscellaneous aspect
Evaluation of pain in preschool children
 Physiological and behavioural
 Self report
 Methods
 Happy sad face scale, the oucher scale, colour analog
scale, poker chip tool, ladder scale, linear analog scale.

35. Evaluation of pain in neonate and children
Physiological and behavioural response
 Physiological changes - ↑ HR, RR, BP, palmer, sweating
 Behavioural changes
 Eyebrow bulge, eye squeeze, nasolabial furrow, open
lips, vertical or horizontal stretching of mouth, lip purse.
 Diffuse body movement
 Type of cry