Pain Flashcards

1
Q

What is nociception?

A

Physiological processing of tissue damaging information

Sensory aspect of pain (Somatosensory Component)

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2
Q

How is pain biologically advantageous?

A

Protective mechanism to prevent tissue injury and permit recovery from injury

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3
Q

What is the international association for the study of pain definition

A

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (it feels like —-)

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4
Q

Define hyperalgesia

A

Heightened pain (eg when damaged tissue is exposed to noxious stimulus)

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5
Q

What is allodynia?

A

Pain arising from gentle touch (painful response to a stimulus that would not normally be painful)

Key feature in chronic pain syndromes

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6
Q

Specific pain pathways allow the _____, _____ and _____ of pain

A

Specific pain pathways allow the localization, intensity and quality of pain

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7
Q

What is the affective component of pain?

A
  • Production of negative emotion
  • Arousal
  • Initiation of stress responses
  • Interruption of ongoing procedures (pain demands attention)
  • Learning - plasticity in painful response
  • Stress, anxiety, anticipation make pain worse (second response worse)
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8
Q

What is musculoskeletal and other ‘mild’ pain?

  • initial response to tissue damage sensed by _________
  • Transmitted by _________ ‘pricking’ pain (first pain)
  • Secondary response; ongoing pain caused by release of _________ _________, _________ and _________ at site of lesion (second pain)
  • Transmitted by _________ - burning, more diffuse pain - slow pain
A
  • initial response to tissue damage sensed by ‘free nerve endings’
  • Transmitted by sensory Adelta-fibres - ‘pricking’ pain (first pain)
  • Secondary response; ongoing pain caused by release of bradykinin, histamine, acid metabolites and prostaglandins at site of lesion (second pain)
  • Transmitted by C-fibres - burning, more diffuse pain - slow pain
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9
Q

What is Deep pain (Nociceptive pain)?

  • Treated with ______
  • deep aching pain, felt as deep to the body surface, poorly ______
  • Initiated by ______
A
  • Treated with opioids
  • deep aching pain, felt as deep to the body surface, poorly localized
  • Initiated by major trauma (post-operative pain, injury or childbirth)
  • both deep pain and mild pain have been referred to as “good pain” - prevent overuse of damaged tissue and allow healing to occur
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10
Q

both deep pain and mild pain have been referred to as “good pain”, why?

A

prevent overuse of damaged tissue and allow healing to occur

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11
Q

What is neuropathic pain?

  • Chronic pain resulting from ___\____
  • Respond poorly to ___\____
  • Treat with ___\____, ___\____ or ___\____ such as ___\____ or ___\____
A
  • Chronic pain resulting from nerve injury or infections
    • phantom limb pain
    • trigeminal neuralgia
    • diabetic neuropathy
    • post herpetic neuralgia (shingles)
    • HIV-AIDS neuropathy
  • Respond poorly to opioids
  • Treat with antidepressants, cannabinoids or anticonvulsants such as pregabalin or gabapentin
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12
Q

What are the most standard frontline treatments for neuropathic pain?

A

Pregabalin or gabapentin

Structurally similar to GABA

*Effect Ca++ channels

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13
Q

Why is chronic, neuropathic pain considered bad pain?

A

No obvious biological function

  • injury should have already been recovered so the continued pain response is unecessary
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14
Q

Neuropathic pain:

  • ______ onset
  • most striking feature:
  • Characterized by ______, _______, _______ and _______
A

Neuropathic pain:

  • slow onset - outlasts original injury
  • most striking feature: Stimulus independent pain
    • Critical because there isn’t a noxious stimuli
  • Characterized by allodynia, hyperalgesia, causalgia, and spontaneous (stimulus independent) pain
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15
Q

Pain Pathways:

  • Afferent (sensory) neurons reside in ______ along spinal cord - send axons out to innervate body surface
  • A-alpha, A-beta fibres:
    • _______ ______ conducting
    • Carry _______ information
    • Convey_____. _____. _____
    • Piezo 2 channels are _______
A

Pain Pathways:

  • Afferent (sensory) neurons reside in dorsal root ganglia along spinal cord - axons innervate body surface
  • Aalpha and Abeta fibres: non-pain fibres
    • Myelinated rapidly conducting
    • Large cell bodies and thick axons - heavily myelinated
    • Carry innocuous information (non-pain)
    • Convey touch, pressure, muscle afferent information
    • Piezo 2 channels are mechanosensors
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16
Q

Which A fibres carry painful stimuli?

A

A-delta

17
Q

A-delta fibres are:

  • Thinly ____ (carry first pain) - slower than A-alpha / A-beta
  • ____ conduction velocity (
  • High threshold ________
  • Terminate primarily in ________ (marginal zone), ________and ________
A

A-delta fibres are:

  • Thinly myelinated (carry first pain)
  • Slow conduction velocity (<40m/sec)
  • High threshold mechanoreceptors (mechanical nociceptors)
  • Terminate primarily in spinal lamina I (marginal zone - superficial region of spinal cord), Lamina II and Lamina V (still upper half (dorsal) spinal cord)
18
Q

The prototypical pain fibres are the ____ fibres

A

C-fibres

19
Q

C-fibres:

  • _____ conduction velocity (0.2-1m/sec) because they are:
    • ___________
  • Terminate primarily in ________
  • Specific Classes:
    • _______
    • __________
A

C-fibres:

  • Very slow conduction velocity (0.2-1m/sec)
  • unmyelinated
  • Terminate primarily in spinal laminae I and II (marginal zone and substantia gelatinosa)
  • Specific Classes:
    • Peptidergic
    • Non-peptidergic (aka Isolectin B4 Positive (IB4+))
20
Q

What are the 2 classes of C-fibres and how are they distinct?

A
  • Specific Classes:
    • Peptidergic - express sensory neuropeptides (substance P/CGRP)
      • High-threshold mechanoreceptors (strong mechanical stimulation)
      • Polymodal nociceptors (noxious heat mechanical stimuli, chemical irritants)
      • Mechanical cold nociceptors (skin cooling)
    • Non-peptidergic (aka Isolectin B4 Positive (IB4+)) - no substance P or CGRP
      • Low threshold mechanoreceptors (gentle mechanical stimulation)
21
Q

Images of Abeta and Adelta

A

Peptidergic C

Non-peptidergic C

22
Q

All sensory fibres release the excitatory amino acid neurotransmitter to transmit their signals:

A

Glutamate

23
Q

A-delta’s and Peptidergic C fibres express, as well as glutamate, ________

A

A-delta’s and Peptidergic C fibres express, as well as glutamate, sensory neuropeptides (Substance P, CGRP)

24
Q

Which afferent fibres only express glutamate?

A

A-alpha and Non-peptidergic C

25
Q

Pain fibre channels to know:

A
  • Nav1.7/1.8/1.9 (sodium channels)
    • Important for AP generation
    • These ones are exclusively on pain fibres
  • TRPV1
    • ion channel that alerts us to things that are hot
    • Heat sensor (capsaicin is endogenous ligand for TRPV1)
    • In C-fibres:
      • Current of TRPV1 in non-peptidergic C is very low
        • sensation of heat/burning likely not carried by Non-P C unless there’s previous trauma (hyperalgesia)
  • IB4 - only on non-peptidergic C (IB4+)
26
Q

Which Afferent fibres express Nav1.7/1.8/1.9?

A
  • A-delta
  • Peptidergic C
  • Non-peptidergic C

ie the pain afferents

27
Q

Which sensory afferents contain TRPV1?

A
  • conveys heat information (capsaicin endogenous ligand)
  • On
    • Peptidergic C
    • A-delta
    • Non-peptidergic C (less current through here though, unless previous trauma)
28
Q

Spinal processing of pain:

  • In dorsal horn, pain fibers project to:
    • _______ (_______)
    • _______ (_______)
    • _______
  • Contact:
    • _______ projection neurons which project to _______, _______, _______ and _______
    • Local circuit interneurons involved in _______ and _______ reflexes
    • Dendrites of wide dynamic range neurons (_______ and _______)
A

Spinal processing of pain:

  • In dorsal horn (posterior), pain fibers project to:
    • Lamina II (substantia gelatinosa)
    • Lamina I (marginal zone) - direct connection (A-delta are so fast)
    • Lamina V - where some mixing of sensations (allodynia)
  • Contact:
    • Lamina I projection neurons (second order neuron) which project to brainstem, parabrachial nucleus, hypothalamus and thalamus
    • Local circuit interneurons involved in local withdrawal and autonomic reflexes
    • Dendrites of wide dynamic range neurons (Lamina IV and V)
29
Q

Peptidergic C fibres project to _______, majority go to ________

A

Peptidergic C fibres project to lamina I, majority go to Outer lamina II (substantia gelatonosa)

30
Q

A-beta myelinated fibres project into _______ and ______

A

A-beta myelinated fibres project into lamina V and lamina III-IV

  • allodynia may be a result of the proximity of Lamina III-IV to lamina I (specifically Inner lamina I) - mixing of signals
31
Q

Glutamate acts on ________ receptors

A

Glutamate acts on excitatory NMDA and AMPA receptors

AMPA is faster (A-delta (lamina I))

32
Q

Substance P and CGRP released by some pain fibres generate __________

A

Substance P and CGRP released by some pain fibres generate slow excitation of dorsal horn cells —- intensify pain response

co-released with glutamate - summation

33
Q

Transmission of neurotransmitters in Dorsal horn is modulated by ________

A

Transmission of neurotransmitters in Dorsal horn is modulated by GABA/glycine interneurons

Inhibitory interneurons - dampen excitatory input

34
Q
  • Some inhibitory interneurons also release _____ and ______ (endogenous opioids)
  • Descending pathways from ________ release endogenous opioids
  • Descending NA/5-HT inputs from areas in brainstem: ________, ________ and ________
    • Modulate ________ of pain
    • 5-HT ________
    • NA predominantly________
A
  • Some inhibitory interneurons also release encephalin and endorphin (endogenous opioids)
  • Descending pathways from Rostroventral medulla (RVM) release endogenous opioids
  • Descending NA/5-HT inputs from rostroventral medulla, locus coereleus (LC) and Raphe nuclei
    • Modulate spinal processing of pain
    • 5-HT mixed excitatory/inhibitory
    • NA predominantly inhibitory
35
Q

Axons to the brain:

Multiple pathways:

  • most axons of lamina I and lamina V projection neurons cross midline and ascend in anterolateral quadrant of spinal cord
  • 5 tracts:
    • Spinothalamic Tract
    • Spinoreticular tract
    • Spinomesencephalic tract (spinoparabrachial tract)
    • Cervicothalamic tract
    • Spinohypothalamic tract
A

Axons to the brain:

Multiple pathways:

  • most axons of lamina I and lamina V projection neurons cross midline and ascend in anterolateral quadrant of spinal cord
  • 5 tracts:
    • Spinothalamic Tract
      • Pain tract
        • Spinal cord to thalamus
    • Spinoreticular tract
      • spinal cord to reticular formation
      • Critical for alerting capacity of pain (stepped on thumbtac and knew immediately)
    • Spinomesencephalic tract (spinoparabrachial tract)
      • layers onto Spinoreticular tract
    • Cervicothalamic tract
    • Spinohypothalamic tract
36
Q

Spinothalamic Tract (medial division): - old

  • project to __________
  • Thalamus = gateway to the __________
  • __________ and __________ aspects of pain
  • Association with __________pain
  • Lacks __________ organization - input comes from __________ have large __________ fields
  • Project widely to __________ and __________ cortex
A

Spinothalamic Tract (Medial):

  • project to intralaminar thalamic neurons
  • Thalamus = gateway to the cortex
  • Affective and alerting aspects of pain
  • Association with slow (second) pain
  • Lacks somatotopic organization - input comes from dorsal horn cells have large receptive fields
  • Project widely to association and prefrontal cortex
37
Q

Spinothalamic Tract (Lateral division) - newer

  • Projects to __________ (__) nucleus of the thalamus
  • __________ organized, __________ and __________ aspects of pain
  • Only __________ of VPL neurons are nociceptive
  • Project to __________ and __________ lobe
  • Associated __________, __________ pain
A

Spinothalamic Tract (Lateral division) - newer

  • Projects to ventroposteriolateral (VPL) nucleus of the thalamus
  • Somatotopically organized, localization and discriminative aspects of pain - finer aspects of pain
  • Only 10% of VPL neurons are nociceptive
  • Project to somatic sensory cortex and parietal lobe
  • Associated fast, first pain (A-delta to Lamina I)