L15 - Pain pathway and mechanisms of pain Flashcards

1
Q

Difference between nociception and pain?

A

 Nociception = reception of signals in the CNS evoked by activation of nociceptors that provide information about tissue damage.

 Pain= subjective perception of aversive sensation from a specific region of the body. An individual can have distinct responses to the same nociceptive stimulus

 Pain has affective and emotional components

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2
Q

Classify types of pain based on site of origin ?

A

a) Somatic
a) i) Superficial pain&raquo_space; Initial or delayed pain
a) ii) Deep pain

b)Visceral

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3
Q

Give examples of Somatic pain and visceral pain?

A

Somatic:
1) Superficial pain (skin on finger, e.g. pinprick, pinching): Initial pain (fast, sharp); Delayed pain (slow, dull, diffuse)

2) Deep pain (connective tissue, bones, joints, muscles in hip, e.g. muscle cramp, headache)

Visceral (viscera, e.g. gall and kidney stones, ulcers, appendicitis): slow, chronic, dull

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4
Q

Structure and modality of nociceptor? Adaptation abilities?

A

Non-specialized free nerve endings (not encapsulated)

Majority = multimodal (some activated by specific stimuli)

all non-adapting

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5
Q

Are nociceptors distributed throughout every tissue of the body?

A

No

A few tissues lack pain endings e.g. neural tissues of brain

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6
Q

Afferent nerve fibers of nociceptors?

A

Two kinds of afferent nerve fibers

• A-δ fibers and C fibers (slower, thinner fibers)

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7
Q

Classify types of nociceptor based on speed of conduction, stimuli and response to stimuli?

A
  1. A-δ:
    - Finely myelinated, thicker = FASTER conduction
    - Intense MECHANICAL or TEMP&raquo_space; Transient Receptor Potential (TRP)&raquo_space; depolarize
    - Localized* sharp pricking; Fast first pain
  2. C:
    - Unmyelinated, thinner = SLOWER conduction
    - POLYMODAL (mechanical, temperature, chemicals)
    - In viscera; normally not activated by noxious stimulus, but their firing threshold is largely reduced by inflammation
    - Burning, DIFFUSE*/ Poorly localized
    - Slow, second pain
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8
Q

Sequence of pain transduction from nociceptor to spinal cord?

A
  • 1st order neuron enter the spinal cord via the dorsal horn
  • Connect to second order neuron in the dorsal horn
  • Cross the midline of spinal cord and ascend to the brain on the contralateral side&raquo_space; spinothalamic tract
  • Nociceptors: mainly connect to projection neurons in laminae I, V and VII in grey matter
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9
Q

Explain why A-δ fibers transduce more localized pain than C fibers?

A

Two neurotransmitters from C-fibers: glutamate and substance P (A-δ fibers use only glutamate)

Substance P: not well reuptake, can DIFFUSE to other 2nd order neurons for diffuse signaling
» poor localization of pain

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10
Q

What pain pathway process occur after injury that helps wound healing?

A

Pain hypersensitivity&raquo_space; ensuring that contact with the injured tissue is minimized until repair is complete

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11
Q

2 types of pain sensitization?

A
  • Allodynia: normally innocuous stimuli may be perceived as pain
  • Hyperalgesia: increased painful sensation to noxious stimuli = CENTRAL or PERIPHERAL SENSITIZATION
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12
Q

Mechanism of Peripheral sensitization in Hyperalgesia?

A
  • Damaged cells release bradykinin and prostaglandin, which activate and/or sensitize nociceptors (+mast cells)
  • Release of substance P and calcitonin gene-related peptide (CGRP) from nociceptor sensory endings; causes plasma extravasation and dilation of blood vessels (neurogenic inflammation)
  • Inflammation further sensitizes nociceptors, making them far more sensitive to stimulation (hyperalgesia)
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13
Q

Hyperalgesia is only felt at the site of injury. True or False?

A

False

Can be primary (felt at the site of stimulation) or secondary (spread to a site remote from the original injury)

Inflammatory factors can diffuse away from site of injury

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14
Q

Mechanism of central sensitization in hyperalgesia?

A
  1. Inflammation&raquo_space; Peripheral exposure to nerve growth factor (NGF) from Mast cells
  2. Retrograde transport of signaling endosomes
  3. Increased transcription of brain-derived neurotrophic factor (BDNF)
  4. Central release of BDNF&raquo_space; Increased excitability of second order neuron in dorsal horn (enhanced synaptic transmission) , reduce stimulus threshold
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15
Q

List all the ascending pathways for pain transduction?

A

Discriminative aspect of pain: Lateral spinothalamic tract

Affective aspect of pain: Spinoreticular tract/ Spinomesencephalic tract

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16
Q

Pathway for discriminative pain?

A

For localization, discrimination (intensity, quality) of pain

  • 1st order neuron at dorsal horn of spinal cord
  • 2nd order neuron corsses spinal cord > lateral spinothalamic tract > medulla, pons, thalamus
  • Reach ventral posterior nuclei (VPL and VPM) of thalamus
  • somatosensory cortex S-I, S-II + Association cortex
17
Q

Pathway for affective pain via Spinoreticular tract?

A
  • To reticular formation (RAS)
  • Medial groups of thalamic nuclei,

> > insular cortex and anterior cingulate cortex (limbic system)

18
Q

Difference in function between Spinoreticular tract and Spinomesencephalic tract?

A

Spinoreticular = autonomic reflex, arousal and emotional aspects of pain

Spinomesencephalic = affective & aversive behavior associated with pain and descending pain modulation

19
Q

Pathway for affective pain via Spinomesencephalic tract?

A

areas of midbrain including periaqueductal gray (PAG) > amygdala

20
Q

Define neuropathic pain?

A
  • Different from central pain sensitization
  • Injuries to the afferent nerves in the peripheral or central pathways&raquo_space; Burning or electrical sensation
  • e.g. shingles
21
Q

Cause and result of Thalamic pain syndrome?

A
  • Lesions in the ventral posterior thalamus due to stroke

* resulted in analgesia followed weeks or months later by paraesthesia (burning, pickling pain)

22
Q

Compare the fiber tracts for pain signal from head, face vs from body, limbs to the thalamus.

A

Head, face = trigeminal nerve&raquo_space; trigeminothalamic system&raquo_space; VPM

Body, limbs = spinothalamic tract&raquo_space; VPL

23
Q

Define pain perception?

A

interpretation of the characteristics of noxious stimuli in terms of :
• Type of pain (submodalities)
• Where (spatial localization)

> > elicit body reaction to pain

24
Q

What are the 2 descending pathways for pain modulation?

A

1) Spinomesenphalic tract:
Cerebral cortex&raquo_space; midbrain periaqueductal gray (PAG)&raquo_space; nucleus raphe magus of the medulla&raquo_space; superficial layers of the dorsal horn.

2) Locus ceruleus tract
noradrenergic locus ceruleus neurons (upper pons)&raquo_space; medulla&raquo_space; dorsal horn laminae

25
What neurotransmitters are used in the 2 descending pathways for pain modulation?
1) Spinomesencephalic tract • Periaqueductal gray (PAG): serotonin, glutamate, opioid neuropeptides • Nucleus raphe magnus: serotonergic 2) Locus ceruleus tract • Locus ceruleus: noradrenergic • Spinal dorsal horn interneurons: enkephalin (opioid)
26
Action of enkephalin released from interneuron in the NE locus cerulus neuron modulatory pathway?
Raphe magnus neuron/ pontine neuron activate spinal dorsal horn interneurons >> release enkephalin: 1) Inhibits release of glutamate and substance P from the presynaptic afferent nociceptor 2) Hyperpolarize postsynaptic second-order neuron >> reduce transduction of pain signals to brain
27
Define the gate control theory in pain modulation.
Local control within spinal cord, doesn't involve the brainstem: filter out low-level pain via interneuron i.e. skin rubbing • Activates Aβ non-receptive mechanoreceptor • Activate interneuron >> Inhibits the pain projection neuron in the dorsal horn
28
Define submodality of pain
Different qualities of pain: sharp, pricking, tearing, crushing, burning, dull, soreness… etc
29
How are submodalities of pain classified? What contribute to these submodalities?
2 classes of nociceptive afferents: - A-δ: sharp, pricking, tearing, crushing - C: burning, dull, soreness Contribution by non-nociceptive modalities - i.e. mechanoreceptive integrate signal with nociceptor - Psychological factors - Learning and experience
30
Explain why pain is not well-localized compared to touch?
* Low innervation density, wide receptive field***** (of nociceptors, neurons of ant. cingulate and insular cortex) * Coarse topographical representation (pain perception cortexes not as well structured as somatosensory cortex) * Branching & convergent ascending fibers (thalamus medial groups have larger receptive field than lateral group for touch)
31
Diseases that arise from errors in spatial coding of pain/ localization?
Phantom limb | Referred pain
32
Explain the mechanism of phantom limb?
pain from amputated limbs: - Reorganization of somatosensory cortex***** (i.e. touch face = feel limb) - Increase in excitability of second order neuron in dorsal horn (central sensitization) = spontaneous firing (surgical amputation causes excessive stimuli to nociceptors, increase NGF and BDNF = hyperactivity)
33
Define referred pain.
Excitation of visceral nociceptors sensed as originating from superficial sites Visceral pain referred to cutaneous dermatomes that share the same dorsal root
34
Define convergence- projection in relation to referred pain.
convergence of nociceptive cutaneous and visceral receptors onto same group of second-or third-order neuron i.e. nociceptors form skin and heart converge at 2nd or 3rd order neuron >> misinterpret pain from diff site
35
Function of Transcutaneous electrical nerve stimulation (TENS)?
stimulate Aβ fibers (gate theory)