PAIN For medical students

2. Prof. Ashraf Abdou
Neuropsychiatry department
Alexandria university

3. Pain
Definition
An unpleasant sensory and
emotional experience associated
with actual or potential tissue
damage or described in terms of
such damage
International Association for the Study of Pain

4. Function of Pain
Pain protects humans by warning of occurrence of
biologically harmful processes
 reflexes, regulated at the level of spinal cord, protect
by removing a body part away from danger
 associated emotional arousal, experienced as distress
or fear, may also motivate a person to move away from
a painful stimulus
 Fear of pain can also prevent a person from moving,
which in turn promotes healing of the injury resulting in
that pain
 pain may elicit an empathic, comforting, and health
promoting behavior in people observing a person in pain.

5. 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

6. Major Categories of Pain
Classified by inferred pathophysiology:
1. Nociceptive pain (stimuli from somatic
and visceral structures)
2. Neuropathic pain (stimuli abnormally
processed by the nervous system)

8. Pain Language
Acute pain: lasts less than 6 months,
subsides once the healing process is
accomplished.
Chronic pain: involves complex
processes and pathology. Usually involves
altered anatomy and neural pathways. It is
constant and prolonged, lasting longer
than 6 months, and sometimes, for life.

9. Types of Somatic Sensations
Musculoskeletal
System
Skin
Pain
Temperature
Proprioception
Touch
Position Sense
Pressure
Vibration
Kinesthesia
Pain

10. Transmission/Perception of Pain
 Four specific parts of
the nervous system
transmit pain signals
from the periphery to
the higher centers of
the CNS:
 the nociceptors,
 the dorsal horn
neurons,
 the ascending tracts,
and
 the supraspinal
projections.
Robinson(1997), Journal of Hand Therapy

11.  Nociceptors, one
type of
somatosensory
receptors, are the
first order neurons of
pain pathways.
 Free nerve endings
 These receptors
generate pain
signals in response
to harmful stimuli.
Nociceptors

12. Nociceptors
Robinson(1997), Journal of Hand Therapy
 Cell bodies of the nociceptors reside in the dorsal
root ganglia (DRG).
 Nerve fibers leaving the DRG bifurcate and send one
branch to the periphery and the other branch to the
dorsal horn (DH).
 The peripheral fibers conduct pain signals from the
skin, muscles, fascia, vessels, and joint capsules to
the DRG

13.  The sensory peripheral fibers, have been classified into three
types based on their diameter, myelination and conduction
velocity: A (with four subtypes – α, β, γ and δ) B and Cfibers.
 A-δ fibers (Myelinated) conduct fast pain (a sensation
experienced immediately after an injury that indicates location of
injury).
 C-fibers (Un-myelinated) conduct slow pain (follows sharp pain
and can be characterized as a dull, throbbing ache with poor
localization).

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 are
interconnected with the hypothalamus and autonomic
nervous system,
the perception of pain is associated
with an autonomic response

16. Interneurons
http://www.amacmeonline.com/pain_mgmt/modul
e01/03patho/index.htm

17. Thalamus contains nerve centers responsible for vision, hearing
reflexes, equilibrium and posture. It also relays pain signals to
the cerebrum. Crude sensation reaches consciousness in the
thalamus, the cerebral cortex is responsible for the higher thought
processes such as emotion and interpretation.

20. Regulation of Pain: Accentuation
 Passive transmission of noxious stimuli cannot explain how
people experience pain. Pain experience can be explained
by an active process.
 This active process includes several regulatory
mechanisms that participate in attenuating or accentuating
the perception of a noxious stimulus.
 An accentuated pain experience can be associated
with factors such as edema, fear, anxiety, and release
of endogenous chemicals that sensitize nerve endings.
 Spinal cord level mechanisms explain an accentuated pain
experience:
 1) allodynia,
 2) wind-up, and
 3) central sensitization.

21. Allodynia
 It occurs when normally
innocuous stimuli begin to
produce pain.
 Following intense, repeated,
or prolonged stimulation, or if
inflammation is present,
 the threshold for primary
afferent nociceptors is
lowered and
 the frequency of firing is
higher for all stimuli.
 Example: cloths become
painful in case of neuropathy

22. Wind-Up
 Low frequency repetitive stimulation of C-fibers
produces a gradual increase in the discharge
 Example: frequently touching the hot plate becomes painful
 In this state there are
 augmented responses to input and
 enlarged receptive fields.
 Input from areas that previously did not activate the WDR neuron
now evoke a prominent response, and
 Low threshold stimulation is able to drive the neurons.
 Wind-up is elicited by any prolonged or intense C-fiber
input.

23. Central Sensitization
 It results in an
increased
responsiveness of the
nociceptive dorsal
horn neurons resulting
in enhanced
conduction of pain
signals to the brain.
 Example: following
injury, an area of
undamaged skin
adjacent to the damaged
tissue can evoke pain
 .

24. Regulation of Pain: Attenuation
 2 classic examples of pain
attenuation.
 First, after injuring a hand, a
person may shake it vigorously
to reduce pain sensation.
 Second, an athlete, although
injured during a game, may not
feel injury related pain until end
of game.
 Regulatory mechanisms that
attenuate pain act at four levels of
the CNS:
1)
the dorsal horn
2)
the descending fibers (from
periaqueductal gray, raphe
nuclei, and locus ceruleus),
3)
hormonal system (
Cerebral
Cortex
Descending
Fibers
Hormonal
System
Dorsal Horn

25. Theory of pain production and modulation
ON GATE CONTROL THEORY (created by Melzack and Wall)
• According to this theory, nociceptive impulses are
transmitted to the spinal cord through large A-δ 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- α, A- β} causes
the cells in SG to
•A
"close the gate".
closed gate decreases stimulation of T-cells (the
2nd afferent neuron), which decreases transmission of
impulses, and diminishes pain perception

26. Gate theory

28. Pain
Factors that lower pain
threshold
Factors that raise pain
threshold
Discomfort
Insomnia
Fatigue
Anxiety
Fear
Sadness
Depression
Boredom
Introversion
Mental isolation
Social abandonment
Relief of symptoms
Sleep
Rest
Empathy
Companionship
Diversional activity
Reduction in anxiety
Elevation of mood
Analgesics
Anxiolytics
Antidepressants

29. Neuropathic Pain

31. Neuropathic Pain
Abnormal processing of the impulses
either by the peripheral or central nervous
system
May be caused by injury (amputation and
subsequent phantom limb pain), scar
tissue from surgery (back surgery high
risk), nerve entrapment (carpal tunnel), or
damaged nerves (diabetic neuropathy)

32. Painful Mononeuropathies and Polyneuropathies
 Diabetic neuropathies
 Entrapment neuropathies
 Postherpetic neuralgia
 Trigeminal and other CNS neuralgias

33. Nociceptive Pain
Neuropathic Pain
PNS
peripheral
nervous
system
Peripheral
PNS
“Healthy”
sensitization
Abnormal
nociceptors
nociceptor
s
Central
CNS Normal
central
transmissio sensitizatio
nervous
system
n
n
Central
Physiologi
c state
Pappagallo M. 2001.
reorganizatio
n
Pathologic
state
CNS

35. The Concept of Total Pain
Physical
Psychological
Total Pain
Spiritual
Social

36. World Health Organization (WHO)
Step Ladder Approach
Severe Pain 7-10/10
Moderate Pain 4-6/10
Mild Pain 1-3/10
ASA, Tylenol,
NSAIDS
Potent opioids (e.g.
morphine) +/non-opioids
Weak opioids +/- nonopioids (e.g. Tylenol #3®)

37. Targets of pain treatment

38. Drugs for Neuropathic Pain
 NSAIDs
 Opiates
 antidepressants
 anticonvulsants
 local anesthetics
 steroids
 other

39. NSAIDs
 Non-steroidal anti-inflammatory drugs
 Reduce synthesis of PGs
 Cox inhibitors (cyclooxygenase)
 Diminish nociceptor activation
 Block peripheral sensitization
 Antipyretic
 Anti-hyperalgesic
 No sedation
39

40. Opioids
 Spinal cord
 Decreasing neurotransmitter release
 Blocking postsynaptic receptors
 Activating inhibitory pathways
 Supraspinal analgesia
 Peripheral analgesia (prevent nociceptor
sensitization)
40

41. Antidepressants
 Tricyclic antidepressants
 Analgesic effects separate from anti-depressant
effects.
 Amitriptyline: most studied, but most side effects
 Nortriptyline & desipramine: better tolerated, less
well studied
 SSRIs: little evidence of analgesic effect.
 SNRI’s
 inhibit both norepinephrine and serotonin reuptake
 efficacy in neuropathic pain syndromes or pain
associated with depression (duloxetine
[Cymbalta®], venlafaxine [Effexor®])

42. Anticonvulsants
 Agents for neuropathic pain
 Carbamazepine
 Gabapentin (Neurontin®)
 Pregabalin (Lyrica®)
 Start low, go slow
 Watch for side effects