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PMCOL 412 > PAIN I > Flashcards

PAIN I Flashcards

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1
Q

Nociception

A

The neural encoding of a noxious stimulus

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2
Q

What is meant when we say that nociception is neurophysiological

A

The stronger the stimulus the higher the frequency of action potentials

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3
Q

Pain

A

An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage

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4
Q

the 2 Properties of pain

A

Salience and valence; applied to nociceptive signal to give us pain

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5
Q

Salience

A

Level of importance or ability to be noticed, ability to interrupt ongoing activity and behaviour

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6
Q

Valence

A

How pleasant or unpleasant it is perceived to be

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7
Q

Acute (first) pain is ___ (good or bad)

A

`Good pain’ serves biological purpose (protection from tissue injury)–to notice and remove yourself from painful stimuli

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8
Q

Bad pain

A

If Injury leads to inflammation causes chronic pain, carried by C-fibers (second pain)

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9
Q

Acute pain is carried by

A

A-delta fibers to the CNS (‘first’ pain)

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10
Q

First pain is ___ to stimulus

A

proportional

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11
Q

Acute pain

A

Nociceptive stimulus, e.g. stepping on a nail, causes acute pain via activation of nociceptive pathways

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12
Q

Chronic Pain Timeline

A

No set time for chronic pain–could be 1 month or a year

Is any stimulus-independent pain

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13
Q

Chronic pain is better described as

A

Stimulus independent pain

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14
Q

Subtypes of Chronic pain

A
  • Mild, musculoskeletal pain
  • Deep pain
  • Neuropathic Pain
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15
Q

Mild, musculoskeletal pain –cause

A

Ongoing pain caused by release of bradykinin, histamine, acid metabolites and prostaglandins

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16
Q

Mild, musculoskeletal pain is ____ to stimulus intensity

A

not proportional

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17
Q

Is Mild, musculoskeletal pain protective?

A

Yes, allow healing

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18
Q

Mild, musculoskeletal pain–treatments

A

Treated with NSAIDs (non-steroidal anti-inflammatory drugs)

ex. aspirin (acetylsalicylic acid) or ibuprofen

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19
Q

Deep Pain–treatments

A

Treated with major analgesics (opioids) such as morphine

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20
Q

Deep pain–localization and def

A

Deep aching pain, deep to body surface, poorly localized

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21
Q

Deep Pain causes

A

Pain associated with major trauma, traffic accident, childbirth, some forms of post operative pain or disease such as heart attack or cancer

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22
Q

Is deep pain beneficial

A

Yes, still ‘good pain’ as it is protective. Allows healing process to progress

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23
Q

Neuropathic Pain-definition

A

pain induced by injury to or disease of the somatosensory system

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24
Q

Neuropathic pain results froom

A

injury to the nervous system

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25
Examples of neuropathic pain
Herpes Zoster --> postherpetic neuralgia (shingles) Phantom limb pain, trigeminal neuralgia, postherpetic, diabetic and HIV-related neuropathies, post-stroke pain, fibromyalgia
26
Timeline of neuropathic pain
Outlasts initial injury, slow onset (develops long after initial acute pain)
27
Is neuropathic pain beneficial
NO, has no obvious protective role | It is "bad pain"
28
Neuropathic pain is characterized by
Spontaneous shooting pain Causalgia Hyperalgesia Allodynia
29
Hyperalgesia--definition
heightened pain sensitivity, same stimulus mode | increased sensitivity to painful stimuli
30
Allodynia--definition
painful response to innocuous stimulus, different stimulus mode, can be touch, cold or warmth (pain to innocuous stimuli)
31
Pain perception has 2 components
Somatosensory component and Affective component
32
Somatosensory Component of pain
Specific pain pathways allow the localization, intensity and quality of pain--how pain is felt (how strong, where, what)
33
Affective component of pain
* Production of negative emotion * Arousal * Initiation of stress responses * Interruption of ongoing procedures (i.e. waking due to pain) * Learning (associating stimuli to pain) * Stress, anxiety, anticipation make pain worse
34
Free nerve endings--what are they
primarily afferent nociceptors; | cutaneous nociceptors
35
Free nerve endings--role
Transduce mechanical, thermal, chemical or tissue damaging stimuli into trains of a.p.’s
36
Free nerve endings stronger stimulus...
stronger stimulus more a.p’s
37
Where are the cell bodies of free nerve endings
Cell bodies in DRG
38
Pathway of free nerve endings
receptors in the skin , cell bodies in DRG --> project to substantia gelatinosa, marginal zone and wide dynamic range neurons in dorsal horn of SC --> brainstem --> thalamus --> somatosensory cortex
39
Primary Afferent fibres
A-alpha and A-beta fibres A-delta fibres C-fibres
40
Properties of A-alpha and A-beta fibres
fast conducting (40-50 m/s) thickly myelinated fibers proprioception touch sensors
41
A-delta fibers
``` myelinated slower conducting (~ 20m/s) high threshold mechanoreceptors--need strong stim (ex. pain stim) for stimulation ```
42
C-fibres
``` unmyelinated slow conducting (< 2m/s) ```
43
2 subtypes of C-fibres
Polymodal nociceptors (peptidergic) and non-peptidergic
44
Polymodal nociceptors
contain neuropeptides (SP and CGRP) and express TRPV1 channels
45
Non-peptidergic
"itch" fibres | bind isolectin B4 (IB4)
46
Damaged tissue or inflammation releases:
``` • NGF (nerve growth factor) • bradykinin (painful when applied) • ATP (leaked from damaged cells) • histamine (inflammatory) • Prostaglandin (from cell memb breakdown) • H+,K+ • 5-HT • Cytokines (IL-6 and IL-1b, TNF-alpha) CAUSES activation of C-fibres ```
47
TRPV1 Receptors
aka Vanilloid receptors | Ligand gated ion channels activated by: warmth etc.
48
TRPV1 Receptors activated by
* Capsaicin (why u sweat when u eat spicy food) * Resiniferatoxin * Moderate thermal stimuli (43 degrees C) * H+
49
TRPA1 Receptor activated by
Noxious heat (> 52 degrees C) on A-delta cells
50
TRPM-8 receptor activated by
``` Noxious cold (8-28 degrees C) Menthol and icilin ```
51
Number of TRP channels
>30
52
Are hot and cold channels on the same cells
sometimes! | different channels but can be expressed on same cells
53
Ionotropic Receptors
* 5HT3 Receptors * P2X3 * ASIC
54
P2X3 receptors
iontropic receptor that is ATP-sensitive and found on sensory neurons
55
ASIC receptor
iontropic receptor that is acid sensitive | activated by H+
56
Metabotropic Receptors
* B2 bradykinin * Eicosanoid (activated by prostaglandins) * Histamine (mainly Hist 1) * 5HT1 and 5HT2 * NK1 (atcivated by substance P)
57
Tyrosine kinase receptors
TrkA, TrkB, cytokine
58
Sensitization
Release of prostaglandins, interleukins, bradykinin, acid metabolites, nerve growth factor sensitize nociceptors beyond site of injury
59
Hyperalgesia is due to _____
sensitization; enhanced response to pain
60
Neurogenic inflammation cause
Axon reflex | C-fibre excitation causes release of substance P and calcitonin gene related peptide (CGRP) --> excite other C-fibres
61
Axon reflex
When C-fibres are activated --> CGRP release --> excites other C-fibres Axon reflex b/c don't need to be connected (use chemical messager--CGRP, substance P)
62
Signs of inflammation
Redness (rubor), swelling (tumor), heat (Calor), pain (dolor)
63
Neurogenic inflammation causes
Vasodilation --> rednesss Extravasation of plasma proteins Edema (as fluid follows proteins)--> swelling
64
In dorsal horn, pain fibers project to
``` Lamina II (substantia gelatinosa) Lamina I (marginal zone) Lamina IV ```
65
Lamina I projection neurons project to
brainstem, parabrachial nucleus (in hypothalamus), hypothalamus and thalamus
66
Local circuit interneurons allow
local withdrawal and autonomic reflexes
67
Pain fibres contact to ___ neurons in the lamina __ and __
The dendrites of Wide dynamic range neurons (WDR); lamina IV and V
68
WDR deferential firing to diff fibres
fire slowly with Ab fibre input (tactile stim= weak) | strongly with Ad fibre input (pain stim = strong)
69
Descending inputs
NA/5HT from rostroventral medulla, LC and raphe nucleus | Modulatory--how mood, etc. can alter pain
70
Primary afferent fibers release
Glutamate; | glut --> acts on NMDAR/AMPAR --> EPSCs
71
Release of P, CGRP and Neurokinin A
Generates slow EPSPs in dorsal horn cells
72
5HT release in dorsal horn
predominantly excitatory
73
NA release in dorsal horn
predominantly inhibitory
74
Transmission in the dorsal horn is modulated
GABA / glycine inhibitory interneurons
75
Sensitization of cutaneous nociceptors and repetitive discharge leads to
sensitization of dorsal horn neurons
76
Sensitization of dorsal horn neurons and plasticity has led to
the pre- emptive use of local anaesthetics (in addition to general anaesthetics) in surgery--to keep sensory nerves quiet to they don't become sensitized and cause pain after surgery
77
Types of Pain
Acute (first) and chronic (second) pain | 2nd pain types: Musculoskeletal, Deep pain, Neuropathic Pain
78
Peripheral Mechanisms
Vanilloid and other receptors role of inflammatory mediators in generating pain Neurogenic inflammation/axon reflex
79
Dorsal Horn in pain
* Integration in substantia gelatinosa * Inputs to laminae I, IV and V * Descending modulation via 5-HT and NA pathways

PMCOL 412 (35 decks)

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