Pathophysiology of pain

1. PATHOPHYSIOLOGY OF PAIN

2. Definition of pain
• Pain is an unpleasant phenomenon that is uniquely
experienced by each individual; it cannot be
adequately defined, identified, or measured by an
observer
Pain is totally subjective

3. Pain Mechanism
Etiological Factors
inflammation/tissue damage/nerve lesions
Pain Syndromes
post-operative/arthritic/back pain/neuropathic

4. Classifications of pain
• Acute
• Chronic
Duration
• Nociceptive
• Neuropathic
• Psychogenic
Pathophysiology
Both classifications can be mixed

5. Acute vs. Chronic Pain
Characteristic Acute Pain Chronic Pain
Cause Generally known Often unknown
Duration of pain Short,
well-characterized
Persists after healing,
3 months
Treatment
approach
Resolution of
underlying cause,
usually self-limited
Underlying cause and
pain disorder; outcome
is often pain control, not
cure

6. Pain types
• Nociceptive pain
Pain transmitted by normal physiologic pathways; via
peripheral nerves to the CNS that is caused by injury to body
tissue. The most common type of this pain is inflammation
• Neuropathic pain
Pain initiated or caused by a primary lesion or dysfunction of
the nerves, spinal cord or brain
• Psychogenic pain
Pain for which there is no known physical cause but
processing of sensitive information in CNS is disturbed

7. NOCICEPTIVE PAIN
EX: INFLAMMATORY PAIN

8. The Fire Inside
• The word “inflammation” traces back to the Latin for “set
afire.”
• Inflammation actually is good in the short run. It’s part of your
immune system’s natural response to heal an injury or fight
an infection. It’s supposed to stop after that. But if it becomes
a long-lasting habit in your body, that can be bad for you.

9. Causes of inflammation
• Can be elicited by numerous stimuli including:
• Infectious agents
• Antigen-antibody interaction
• Ischemia
• Thermal and physical injury

10. Characters of inflammation
• Redness vasodilation of capillaries to increase blood flow
• Heat vasodilation
• Pain Hyperalgesia, sensitization of nociceptors
• Swelling Increased vascular permeability (microvascular structural
changes and escape of plasma proteins from the bloodstream)
• Loss of function
and
Inflammatory cell transmigration through endothelium and accumulation
at the site of injury

12. Mediators of Inflammation
• Vasoactive amines (Histamine, Serotonin)
• Platelet activating factor (PAF)
• Complement system
• Kinin system
• Cytokines
• Nitric oxide
• Adhesion Molecules
• Arachidonic acid metabolites: mediated by cyclooxygenases (COX)
- Prostaglandins (PGs) - Thromboxane A2 (TXA2)
- HETE (hydroxy-eicosatetraenoic acid) - Leukotrienes (LTs)

13. Damage of the cell
releases
Acted upon by
By
By

14. Two main forms of Cyclooxygenases (COX)
Cyclooxygenase-1 (COX-1)
• Produces prostaglandins that
mediate homeostatic functions
• Constitutively expressed
• Plays an important role in
- Gastric mucosa
- Kidney
- Platelets
- Vascular endothelium
Cyclooxygenase-2 (COX-2)
• Produces prostaglandins that
mediate inflammation, pain, and
fever.
• Induced mainly in sites of
inflammation by cytokines

15. Nociceptive pain may be somatic or visceral
15

16. NEUROPATHIC PAIN

17. Definition of Neuropathic Pain
• Pain resulting from or thought to be resulting
from a disturbance of the central or
peripheral nervous system

18. Mechanism of neuropathic pain
• The exact mechanism is not known as the responses to
peripheral nerve damage are complex in nature.
• It is probable that an inter‐related group of mechanisms
contribute to the generation of neuropathic pain in any
given patient, with peripheral, spinal and brain events
possibly all playing a role

19. Pain comes in the form of:

20. Common causes of neuropathic pain
• Diabetic neuropathy
• Post herpetic neuralgia
• Cervical and lumbar radiculopathy
• Post thoracotomy, post mastectomy
• Multiple sclerosis
• Post-stroke
• Phantom limb

21. Most likely neuropathic pain
• Vulvar pain
• Interstitial cystitis
• Atypical facial neuralgia
• Fibromyalgia

22. Neuropathic pain a component
• Post-inguinal hernia
• Osteoarthritis of knee
• Post Total Major Joint(TMJ) replacement

23. Presentation of Pain types
Neuropathic
pain
- Peripheral
- Central
Nociceptive
pain
Mixed
pain
Examples:
PHN
Trigeminal N
DPN
Post surgical N
Post traumatic N
Post stroke pain
Inflammation pain
Fracture pain
Joint pain as in OA
Post operative
visceral pain
- Low back pain
with radiculopathy
- Cervical
Radiculopathy
- Cancer pain
- Carpal tunnel
syndrome
It comes as burning, tingling,
Hypersensitivity to touch or cold
It comes as aching, sharp,
or throbbing

24. 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
• The pain tolerance is expressed as duration of time or the
intensity of pain that an individual will endure(bear/stand)
before initiation overt pain responses.

25. • 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

26. Pain terminology
• Allodynia is a pain due to a stimulus which does not
normally provoke pain and can be either thermal or
mechanical(touch)
• Hyperalgesia is an increased sensitivity to pain, which may
be caused by damage to nociceptors or peripheral nerves
• Hyperpathia is exaggerated reaction to stimuli that normally
cause pain, the feeling of pain continues even after the
stimulus that causes it has been removed.
• Paresthesia pain feeling without touching and no stimulus. An
abnormal sensation, typically tingling or pricking (“pins and needles”), caused chiefly by pressure on or damage to peripheral nerves

27. Pathway 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

28.  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 fibres connecting the reticular
formation, midbrain, and substantia gelatinosa, are responsible for
modulating pain sensation(efferent analgesic system)
Endorphins ("endogenous morphine") are endogenous opioid peptides that function as neurotransmitters.
They are produced by the pituitary gland and the hypothalamus during exercise, excitement, pain,
consumption of spicy food, love and orgasm, and they resemble the opiates in their abilities to produce
analgesia and a feeling of well-being.

29. Physiology of Pain Perception
Injury
Descending
Pathway
Peripheral
Nerve
Dorsal
Root
Ganglion
C-Fiber
A-beta Fiber
A-delta Fiber
Ascending
Pathways
Dorsal
Horn
Brain
Spinal Cord

30. Responses of the body to pain
Responses to acute pain
- increased heart rate
- increased respiratory rate
- elevated blood pressure
- pallor or flushing, dilated pupils
-  blood flow to the viscera, kidney and skin
- nausea occasionally occurs
- diaphoresis
-  blood sugar
-  gastric acid secretion
-  gastric motility
Psychological and behavioural response to acute pain
- fear
- general sense of unpleasantness or unease
- anxiety

31. Impact(effect) of Chronic Pain
Social Consequences
• Marital/family
relations
• Intimacy/sexual activity
• Social isolation
Socioeconomic
Consequences
• Healthcare costs
• Disability
• Lost workdays
Quality of Life
- Physical functioning
- Ability to perform
activities of daily living
- Work
- Recreation
Psychological Morbidity
- Depression
- Anxiety, anger
- Sleep disturbances
- Loss of self-esteem

32. Assessing the Patient With Pain
• Onset and duration
• Location/distribution
• Quality
• Intensity
• Aggravating/relieving factors
• Associated features or secondary signs/symptoms
• Associated factors
– mood/emotional distress
– functional activities
• Treatment response

33. Pain Intensity Rating Scales
• Visual Analogue Scale (VAS)
No pain ----------------------------------- Worst pain
• Categorical Scale
None (0) Mild (1 – 4) Moderate (5 – 6) Severe (7 – 10)
• Numerical Rating Scale
0-------------------------------------------------
No pain
10
Worst pain
imaginable
(Cleeland, 1991; Jacox et al, 1994)

34. THE GOOD : ACUTE PAIN
THA BAD: Persistent nociceptive Pain
THE UGLY: Neuropathic Pain

35. SOME CLINICAL CONDITIONS
ASSOCIATED WITH NEUROPATHIC PAIN

36. 1)Diabetic Neuropathy
• The most common of all the late complications of diabetes
mellitus
• Cause of much suffering in patients with painful neuropathy
• Complications: foot ulcerations, gangrene, amputations,
sexual dysfunction, sudden death from cardiac arrhythmias
• The most common form that occur in 80% of diabetic
patients is called Peripheral Sensorimotor Polyneuropathy(
or simply peripheral neuropathy)

37. Signs and symptoms of Peripheral Sensorimotor
Polyneuropathy
Distal, bilateral,symmetrical, stocking-glove distribution.
Symptoms range from numbness to severe pain. Burning,
alteration of temperature sensation, parathesias, shooting, or
stabbing pains are common.
May worsen at night.
Minor motor involvement causing weakness.

38. Electrophysiological imaging
Normal
Metabolic syndrome
Diabetes

39. 2)Post-herpetic neuralgia
Herpes Zoster:
• Acute, localized infection of the Varicella-Zoster virus, which
causes a painful blistering, pruritic rash.
Post-Herpetic Neuralgia:
• Pain that persists for more than 1 month after the onset of
Herpes zoster.

40. Clinical Presentation of PHN
• Pain that persists for more than a month following the onset of
Herpes Zoster.
• Pain may last months or in a few cases over a year.
• Pain is described as lancinating, burning, shooting, stabbing,
paroxysmal or electrical.
• Allodynia occurs.( pain in reaction to a non- noxious stimuli, light
touch, clothing).
• Pain can be debilitating and interfere with daily functioning .
• Pain ↑ through out the day
• Pain has 2 components : 1) Central , 2) Peripheral.
JAMA (2005), Pain (2006)

41. 3) ORTHOPEDIC DISORDERS

42. 3.1- Carpal tunnel syndrome
• The carpal tunnel is a narrow
passageway of ligament and
bones at the base of the hand.
It contains nerve and tendons.

45. 3.2- Spinal stenosis
• Spinal stenosis is a narrowing in the space of vertebrae
that carries spinal cord and the nerves to arms and legs.
• This space is normally very small, and many different
diseases and conditions can make the canal get even
smaller. Arthritis, falls, accidents, and wear and tear on
the bones and joints in the spine play a part in stenosis.
• As the spinal canal shrinks, the nerves that go through
it are squeezed. This squeezing may cause pain,
numbness, tingling, weakness or clumsiness in your
neck, back, arms, or legs. Many adults have this kind of
stenosis.

46. 3.3- Radiculopathy
• Radiculopathy is irritation of a nerve near spine
• This can be caused by a disc herniation, bone
spur, or tumor that presses on a nerve root
• Radiculopathy can occur in any part of the
spine, but it is most common in the lower back
(lumbar radiculopathy) and in the neck (cervical
radiculopathy).
• It is less commonly found in the middle portion
of the spine (thoracic radiculopathy).

47. Symptoms of Radiculopathy
• The most common symptoms of radiculopathy are pain,
numbness and tingling in the arms or legs.
• It is common for patients to also have localized neck or back
pain as well.
• Lumbar radiculopathy that causes
pain that radiates down a lower
extremity is commonly referred to
as sciatica

48. 3.4- Spondylosis
• What is spondylosis?
• This is just a fancy word for osteoarthritis of the spine. The
arthritis can cause bone spurs (osteophytes), deterioration of
the discs (the shock absorbers) between your vertebrae,
and/or damage to the facet joints that connect the vertebrae.
Any of these can cause stenosis of your spinal canal.

49. 4- Fibromyalgia(FM)?
• FM is a common chronic widespread pain condition
– FM patients often have heightened sensitivity to pain
(hyperalgesia); in addition, nonnoxious stimuli may result in
pain (allodynia)
– Patients may present with a wide range of additional
symptoms including tenderness, sleep disturbances, fatigue,
morning stiffness, cognitive complaints, and mood disorders
FM = fibromyalgia.
Wolfe et al. Arthritis Rheum. 1995;38:19-28; Staud and Rodriguez. Nat Clin Pract Rheumatol. 2006;2:90-98; Wolfe et al. Arthritis Rheum. 1990;33:160-
172; Henriksson. J Rehabil Med. 2003;(suppl 41):89-94.

50. TENDERNESS
• Presence of tender
points≥11points
• Most patients also have
tenderness to pressure, heat,
cold, electrical pain
SLEEP DISTURBANCES
• Characterized by nonrestorative
sleep and increased awakenings
• Abnormalities in the continuity of
sleep and sleep architecture
• Reduced slow-wave sleep
• Abnormal alpha wave intrusion in
non-REM sleep
WIDESPREAD PAIN
• Chronic, widespread pain is
the defining feature of FM
• Patient descriptors of pain
include: aching, exhausting,
nagging, and hurting
FATIGUE/STIFFNESS
• Morning stiffness and fatigue are
common characteristics of FM
Clinical Features of Fibromyalgia
Wolfe et al. Arthritis Rheum. 1995;38:19-28; Leavitt et al. Arthritis Rheum. 1986;29:775-781; Wolfe et al. Arthritis Rheum. 1990:33:160-172;
Roizenblatt et al. Arthritis Rheum. 2001;44:222-230; Harding. Am J Med Sci. 1998;315:367-376.

51. MANAGEMENT OF PAIN

52. BRAIN
Pharmacologic Agents
Affect Pain Differently
Descending Modulation
Central Sensitization
PNS
Local Anesthetics
Analgesics
Anticonvulsants
Tricyclic Antidepressants
Opioids
Anticonvulsants
Opioids
NMDA-Receptor Antagonists
Tricyclic/SNRI Antidepressants
Anticonvulsants
Opioids
Tricyclic/SNRI Antidepressants
CNS
Spinal
Cord
Peripheral
Sensitization
Dorsal
Horn
Decrease inflammatory
response. NSAIDS, local
anesthetics, steroids
Decrease conduction gabapentin,
carbamazepine,local anesthetics,
opioids
Prevent centralization
opioids, ketamine,alpha 2
agonists.
Increase inhibition..
Amitryptiline venlafaxine,
clonidine
Modify expression..anxiolytics

53. Thank you for
your attention!
Any Questions?