Patho physiology of pain

2. • 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”.

3. • “The fifth vital sign” – American Pain Society 2003
• Identifying pain as the fifth vital sign suggests that
the assessment of pain should be as automatic as
taking a patient’s BP and pulse
 Pain is the most COMMON reason patients seek
medical advice
 Pain is a protective mechanism or a warning to
prevent further injury

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) A myelinated nerve fibers
b) C unmyelinated nerve fibers
Points A 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
6) Specific stimulus More sensitive to
pressure
Chemical agents
e.g. LA, Histamine, kinins, PG
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 450C 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, -endorphins
Glutamate Norepinephrine, adrenaline
Aspartate GABA
ATP Glycine
Chemical mediators of pain acting on CNS

9. Pain threshold and pain tolerance
The pain threshold is the point at which a stimulus is perceived
as pain
It does not vary significantly among healthy people or in the same
person over time
Perceptual dominance- intense pain at one location may cause
an increase in the pain threshold in another location
• The pain tolerance is expressed as duration of time or the
intensity of pain that an individual will endure before initiation
overt pain responses.
It is influenced by - persons cultural prescriptions
- expectations
- role behaviours
- physical and mental health

10. • Pain tolerance is generally decreased:
- with repeated exposure to pain,
- by fatigue, anger, boredom, apprehension,
- sleep deprivation
• Tolerance to pain may be increased:
- by alcohol consumption,
- medication, hypnosis,
- warmth, distracting activities,
- strong beliefs or faith
Pain tolerance varies greatly among people and in
the same person over time
A decrease in pain tolerance is also evident in the elderly,
and women appear to be more tolerant to pain than men

11. Age and perception of pain
• Children and the elderly may experience or express pain
differently than adults
• Infants in the first 1 to 2 days of life are less sensitive to pain
(or they simply lack the ability to verbalise the pain experience).
• A full behavioural response to pain is apparent at 3 to 12 month of
life
• Older children, between the ages of 15 and 18 years, tend to
have a lower pain threshold than do adults
• Pain threshold tends to increase with ageing
• This change is probably caused by peripheral neuropathies and
changes in the thickness of the skin

12. Neuroanatomy of pain
The portions of the nervous system responsible for the
sensation and perception of pain may be divided into three
areas:
1. afferent pathways
2. CNS
3. efferent pathways
The afferent portion is composed of:
a) nociceptors (pain receptors)
b) afferent nerve fibres
c) spinal cord network

13.  Afferent pathways terminate in the dorsal horn of the spinal cord
(1st afferent neuron)
● 2nd afferent neuron creates spinal part of afferent system
 The portion of CNS involved in the interpretation of the pain signals
are the limbic system, reticular formation, thalamus, hypothalamus
and cortex.
● The efferent pathways, composed of the fibers connecting the
reticular formation, midbrain, and substantia gelatinosa, are
responsible for modulating pain sensation

15. The brain first perceives the sensation of pain
• The thalamus, sensitive cortex :
perceiving
describing of pain
localising
• Parts of thalamus, brainstem and reticular formation:
- identify dull longer-lasting, and diffuse pain
• The reticular formation and limbic system:
- control the emotional and affective response to pain
Because the cortex, thalamus and brainstem areinterconnected
with the hypothalamus and autonomic nervous system, the
perception of pain is associated with an autonomic response

16. The role of the afferent and efferent pathways in
processing of pain information
Nociceptive pain
Nociceptors: Endings of small unmyelinated and lightly
myelinated afferent neurons
Stimulators: Chemical, mechanical and thermal noxae
Mild stimulation  positive, pleasurable sensation
(e.g. tickling)
Strong stimulation  pain
These differences are a result of the frequency
and amplitude of the afferent signal transmitted
from the nerve endings to the CNS
Location: In muscles, tendons, epidermis, subcutanous tissue,
visceral organs
- they are not evenly distributed in the body
(in skin more then in internal structures)

17. Afferent pathways:
• From nociceptors  transmitted by small A-delta fibers and
C- fibers to the spinal cord  form synapses with neurons
in the dorsal horn(DH)
• From DH  transmitted to higher parts of the spinal cord
and to the rest of the CNS by spinothalamic tracts
*The small unmyelinated C- neurons are responsible for the
transmission of diffuse burning or aching sensations
*Transmission through the larger, myelinated A- delta fibers
occurs much more quickly. A - fibers carry well-localized,
sharp pain sensations

18. Efferent analgesic system
Its role: - inhibition of afferent pain signals
Mechanisms:
- pain afferents stimulates the neurons in periaqueductal
gray (PAG) - gray matter surrounding the cerebral
aqueduct in the midbrain results in activation of efferent
(descendent) anti-nociceptive pathways
- from there the impulses are transmitted through
the spinal cord to the dorsal horn
- there thay inhibit or block transmission of nociceptive
signals at the level of dorsal horn

19. The role of the spinal cord in pain processing
• Most afferent pain fibers terminate in the dorsal horn of the
spinal segment that they enter. Some, however, extend
toward the head or the foot for several segments before
terminating
• The A-  fibers, some large A-delta fibers and small C- fibers
terminate in the laminae of dorsal horn and in the substantia
gelatinosa
• The laminae than transmit specific information (about
burned or crushed skin, about gentle pressure) to 2nd
afferent neuron

20. • 2nd afferent neurons transmit the impulse from the substantia
gelatinosa (SG) and laminae through the ventral and lateral horn,
crossing in the same or adjacent spinal segment, to the other side
of the cord. From there the impulse is carried through the
spinothalamic tract to the brain. The two divisions of
spinothalamic tract are known:
1. the neospinothalamic tract - it carries information to the mid brain,
thalamus and post central gyrus (where pain is perceived)
2. the paleospinothalamic tract - it carries information to the
reticular formation, pons, limbic system, and mid brain
(more synapses to different structures of brain)

22. Theory of pain production and modulation
• Most rational explanation of painproduction and modulation
is based on gate control theory (created by Melzack and Wall)
• According to this theory, nociceptive impulses are
transmitted to the spinal cord through large A- delta and
small C- fibers
• These fibers create synapses in the SG
• The cells in this structure function as a gate, regulating
transmission of impulses to CNS
Stimulation of larger nerve fibers (A-alfa, A-beta) causes
the cells in SG to "close the gate".
• A closed gate decreases stimulation of T-cells (the 2nd
afferent neuron), which decreases transmission of impulses,
and diminishes pain perception

23. Stimulation of small fiber input inhibits cells in SG and
"open the gate".
• An open gate increases the stimulation of T-cells 
 transmission of impulses  enhances pain perception
• In addition to gate control through large and small fibers
stimulation, the central nervous system, through efferent
pathways, may close, partially close, or open gate.
Cognitive functioning may thus modulate pain perception
Action of endorphins(ED)
All ED act by attaching to opiate receptors on the plasma
membrane of the afferent neuron. The result than is
inhibition of releasing of the neurotransmitter, thus
blocking the transmission of the painful stimulus

25. 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.

26. 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.

27. 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

28. 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.

29. 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

30. 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

31. 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

32. 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
2) Signal of organic disease
process
2) No such function serve
3) Usually caused by noxious
stimulation
3) Cause is often unclear. Psychological
and environmental factors play major role
4) Associated with potent
neuroendocrinal response
4) Absent
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

33. Fast Pain
 A 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.

34. 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

35. 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.
b) Deep somatic pain
• Muscle, joints, bones and fascia.
• Similar to slow pain.
 Clinical condition
• Injuries
• Tissue ischaemia
• Inflammation of tissues
• Muscle spasm

36. 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

37. • Acute pain is a protective mechanism that alerts the
• individual to a condition or experience that is immediately
• harmful to the body
• Sudden onset
Relief - after the chemical mediators that stimulate the nociceptors,
are removed
• This type of pain mobilises the individual to prompt action to
relieve it
• Stimulation of autonomic nervous system can be observed during
this type of pain (mydriasis, tachycardia, tachypnoe, sweating,
vasoconstriction)
• Psychological and behavioural response to acute pain
- fear
- general sense of unpleasantness or unease
- anxiety

38. • Chronic pain is persistent or intermittent usually defined as
lasting at least 6 months
• The cause is often unknown, often develops insidiously, very
often is associated with a sense of hopelessness and
helplessness. Depression often results

39. Psychological response to chronic pain
Intermittent pain produces a physiologic response similar to acute
pain.
Persistent pain allows for adaptation (functions of the body are
normal but the pain is not reliefed)
Chronic pain produces significant behavioural and
psychological changes
The main changes are:
- depression
- an attempt to keep pain - related behaviour to a minimum
- sleeping disorders
- preoccupation with the pain
- tendency to deny pain