Mechanisms Of Pain Flashcards
(77 cards)
1
Q
pain definition
A
unpleasant sensory and emotional experiences associated with actual or potential tissue damge
2
Q
pain is essential for
A
survival and health of animal
3
Q
perception of pain is
A
subjective, affected by emotion and experience and environment
4
Q
acute pain generally elicits
A
strong activation of autonomic reflexes with noticeable change in heart rate and blood pressure; vomiting also common with visceral pain
5
Q
behavioral responses to pain
A
avoidance response or aggression towards subjects inflicting pain often observed
6
Q
chronic pain can manifest as
A
changes in mood, appetite loss, depression
7
Q
pain sensation is a
A
- complex neurological process of both peripheral and central nervous systems, pain scale, and efficacy of analgesics vary from patient to patient
- extent of pain experience dependent
8
Q
pain classified into 3 different types based on mechanisms
A
- nociceptive pain
- inflammatory pain
c. pathologic pain
9
Q
nociception
A
one of somatosensory modalities; critical for detection and avoidance of noxious stimuli
10
Q
nociception threshold
A
high threshold pain activated in presence of intense stimuli playing role in early warning physiological protective system
11
Q
nociceptive pain clinically
A
easily localized not clinically a problem bc anesthetics and analgesics can reduce unpleasant feeling
12
Q
nociceptive stimuli include
A
- extreem heat
- extreem cold
- chemical irritants
- intense mechanical force
13
Q
nociceptive input is not
A
always perceived as pain even when noxious stimuli exist bc could be overwritten by other brain activities such as emotions or experience
14
Q
inflammatory pain
A
- upon tissue injury cells of innate immune system migrate toward site of injury and release proinflam cytokines and small moelecues
- can be spontaneous pain
- pain hypersensitivity
- different inflammatory mediators= sensed by different receptors, inflammatory mediators= trigger for pain sensation
15
Q
“inflammatory soup” fx
A
activate receptors on nociceptor neurons which either evoke action potentials to elicit pain signaling or modulates ion channel properties (often making nociceptors more excitable)
16
Q
inflammatory pain fx
A
protect injured area (persistent warning system)
17
Q
inflammatory pain threshold
A
low threshold pain
18
Q
inflammatory pain treatment
A
NSAIDs often suppress it
19
Q
chronic pain
A
- unnecessarily-prolonged inflammatory pain can become debilitating chronic pain (ex rheumatoid arthritis, lower back pain, sever injury); this is v hard to treat
- pathologic pain is debilitating type chronic pain
20
Q
pathological pain function
A
there isn’t one it isn’t protective
21
Q
pathological pain subclassifications
A
- dysfuncitonal
- neuropathic pain
22
Q
dysfunctional pain
A
substantial pain w/o noxious stimulus or peripheral inflammatory pathogens
23
Q
dysfunctional pain conditions
A
- fibromyalgia
- IBS
- tension type headache
- TMJ dx
- interstitial cystitis
24
Q
neuropathic pain cause
A
neurons themselves are injured and pain hypersensitivity becomes persistant; generally caused by nerve injury
- (ex. back pain, neck pain, migraine, pain after limb amputation)
25
neuropathic pain can occur
spontaneously and duration and amplitude of its response to noxious stimuli are amplified and often irreversible (neuropathic pain = autonomous dx state of nervous system)
26
mechanism neuropathic pain
unclear
27
examples neuropathic pain vet species
- pain from lumbosacral lesions
- intervertebral disc herniation
- other spinal cord injuries
- discospondylitis
- vertebral osteomyelitis
- polyradiculoneuritis
- feline orofacial pain syndrome
28
painpathway
1. transduction
2. transmission
3. projeciton
4. perception
5. modulation
29
transduction
noxious stimuli recognized by nociceptors
30
transmission
nociceptive signals propagate as action potentials
31
projection
signals from nociceptors relayed to neurons in DH spinal cord -> transmitted to brainstem and thalamus
32
perception
thalamic nuclei relay nociceptive info to cerebral cortex, perception pain regulated by non-nociceptive afferent fibers
33
modulation
pain pathway plastic and modulated at many places in pain pathway can -> hypalgesia or analgesia
34
nociceptors types
- As= thinly myelinated (conduction speed 5-30m/s)
| - C fibers- unmyelinated (conduction speed 1m/s)
35
speed nociceptors
slower conduction than touch or proprioception
36
nociceptor structure
- free nerve endings in skin, muscle, jt, bone, viscera
- cell bodies at DRG or trigeminal ganglia
- pseudo unipolar
- central and peripheral terminals emanate from common axonal stalk
37
signal transduction direction nociceptor
bidirectional signal transduction made possible by majority of proteins synthesized in nociceptor neurons distributed to central and peripheral terminals
38
types nociceptors
- thermal nociceptors
- mcechnaicla nociceptors
- polymodal nociceptors
- silent nociceptors
39
thermal nociceptors
- activated >45 C <5C
| - As fibers
40
mechanical nociceptors
- intense pressure activated
| - As
41
polymodal nociceptors
- activated by high intensity mechanical, chemical, or thermal stimuli
- C fibers
42
silent nociceptors
- usually not responsive to noxious stimuli
- responsive upon inflammation and various chemical agents in viscera
- C fibers
43
primary neurotransmitter of primary sensory neurons
glutamate
44
cot transmitters of nociceptors
neuropeptides released as cotransmitters by many nociceptors
45
neuropeptides vs neurotransmitters
no efficient mechanism peptide reuptake so neuropeptides diffuse greater distances than glutamate which can -> poorly localized character of many pain conditions
46
molecular sensors detecting noxious stimuli location
expressed in peripheral terminals of nociceptors
47
molecular sensors for detecting noxious stimuli are often
nonselective cation channels whose activation leads to membrane depolarization, a voltage change called "generator potential" or "receptor potential"
48
steps molecular sensors for detecting noxious stimuli
1. Nonselective cation channels activated -> membrane depolarization (voltage change called generator potential or receptor potential)
2. Voltage-gated Na+ channels
3. action potential
49
each nociceptor tends to express
one class transduction receptors; segregation of diff molecular transducers into distinct subclasses sensory fibers allow peripheral nervous system to elicit specific types pain sensation = helps shape specific avoidance responses
50
ion channels sense different
noxious stimuli
51
what sense noxious stimuli
1. Thermal sensors
2. Chemical sensors
3. Mechanical sensors
52
Thermal sensors
- thermal stimuli sensed by transient receptor potential (TRP) channels
- open and close at different temperatures ranging from 0-60C
- opening TRP allow cations to flow in -> action potential
53
thermal sensors respond to
- diff temperatuers
- natural products (capsaicin, menthol)
- membrane stretch
* they are versatile sensors for all 3 types noxious stimuli)
54
birds thermal sensors
relatively insensitive TRPV1 channels so more tolerant to high temperature and capsaicin
55
chemical sensors
nociceptors can sense
- pungent chemicals (methol capsaicin)
- cellular components (ATP, signaling peptides like calcitonin gene-related peptide), or acid
- chemical sensors are diff ligand gated channels that sense different stimuli
- at peripheral nerve sites chemicals bind to receptors -> action potential; can have modulators modulate excitability of channel
56
chemical sensors include
- TRP channels
- Acid-sensing ion channels (ASICs)
- ionotropic purinergic receptors (P2X receptors)
- receptor tyrosine kinases (ex. TrKA)
- GPCRs
57
activation TRP channels and ligand-gated ion channels
directly evokes generator potentials
58
activation of receptor tyrosine kinases and GPCRs
do not directly trigger action potential but modulate ion channels in nociceptor neurons
59
mechanical sensors
- mechanosensing mechanisms poorly understood; some ion channels demonstrated to sense mechanical stimuli (not necisarrily painful stimuli) including:
- TRP channels
- candidate mechanosensors= 2 pore K+ channels (K2P), Mac-Like mechanosensitive channels, epithelial Na+ channels (ENaC/DEG), Piezo channels
60
nociceptor input and central nociceptive pathways
nociceptor input can trigger prolonged increase in excitability and synaptic efficacy of neurons in central nociceptive pathways (pain sensitization including hyperalgesia, allodynia, and wind up)
- PNS and CNS cause pain sensation
61
abnormal sensitization of pain can ->
maladaptive chronic pain
62
hyperalgesia
- increased pain sensitivity
- primary hyperalgesia st site injury peripheral and central sensitization mechanisms involved
- secondary hyperalgesia- area adjacent to or remote to site injury this is solely due to changes in central processing NOT sensitization nociceptive nerve endings
63
allodynia
- pain in response innocuous stimulis
- occurs when pain pathway hijacked by other sensory pathway via nerve rewiring
- generally pain evoked by AB fibers
64
pain wind up
- in response to repetitive stimulation primary afferent C-fibers
- in absence of intention inflammation, trauma, nerve injury
- underlying mechanism unclear
65
peripheral sensitization
- reduced threshold and increased responsiveness of nociceptor evoked by set of inflammatory mediators released from injured and inflammatory cells
- broad range inducers (usually inflammatory get intracellular cascade of kinases that up regulate signals)
- multiple intracellular signal transduction pathways are involved (mechanotropic receptors turn on intracell signals that indirectly up regulate channels)
- usually inflammatory pain
66
central sensitization
- process that establishes state of hyper-excitability established in CNS -> enhanced processing nociceptive (pain) messages
- C fiber -> interneuron -> brain -> pain
- increase activity Ca2+ channels, increase neurotransmitter please
- kinases can up regulate receptors
67
mechanisms implicated in central sensitization
1. alteration in glutamatergic neurotransmission/ NMDA receptor-mediated hypersensitivity
2. Loss of tonic inhibitory controls (disinhibition)
3. Glial-neuronal interactions
68
nerve termini of sensitized nociceptors release
substance P and calcitonin gene-related peptide (CGRP) which triggers release of inducers from immune cells in peripheral sensitization
69
can have unpleasant stimuli
that isn't perceived as pain
70
protective pain
- acute nociceptive pain
| - acute inflammatory pain
71
debilitating pain
- chronic inflammatory pain
| - chronic pathologic pain (neuropathic/ dysfunctional)
72
site of moduation
synapses; mainly glutaminergic in sensory system
73
neuropathic pain main points
- normally caused by nerve injury
- low-threshold pain
- pain hypersensiitivy
- abnormal central processing
- spontaneous pain
- no appropriate treatments yet
- chronic pain (debilitating and devastating)
74
inflammatory pain main points
- low threshold pain
- pain hypersenstiivty
- spontaneous pain
- fairly effective treatments available (NSAIDs)
- persistence warning system (protective) OR
- chronic pain (debilatating)
75
central sensitization inhibitory interneuron
can inhibit this then inhibition inhibited -> increase sensitization
76
central sensitization microglial activation
have membrane proteins that release cytokines which activate receptors; multiple mechanisms can -> similar symptoms
77
touch pathway in allodynia
goes through sensitized pain pathway and touch is then felt as pain
