Pain System 1 Flashcards
What is pain according to the International Association for the Study of Pain (IASP)?
“An unpleasant SENSORY AND EMOTIONAL experience associated with ACTUAL OR POTENTIAL tissue damage, or described in terms of such damage.”
nociception
physiological processing of tissue damaging information
Why does pain exist in our biology?
protective mechanism to prevent tissue injury and permit recovery from injury
hyperalgesia
heightened pain (e.g. when damaged tissue is exposed to noxious stimulus)
TRUE or FALSE: a sunburn is an example of allodynia
FALSE: hyperalgesia
Draw and label allodynia and hyperalgesia on a pain sensation vs stimulus intensity graph.
slide 5
allodynia
pain arising from gentle touch (painful response to a stimulus that would not normally be painful)
TRUE or FALSE: allodynia is paradoxical pain
TRUE
What are the 2 components of pain perception?
- somatosensory component
- affective component
Describe the 2 responses of musculoskeletal and other mild pain.
- initial response to tissue damage sensed by free nerve endings (pricking pain = first pain)
- secondary response is ongoing pain caused by release inflammatory soup at site of lesion (burning/diffuse pain = second pain)
What fiber transmits first pain
sensory A-delta fibers
What fiber transmits second pain?
C fibers
What is another name for nociceptive pain?
deep pain
What is deep pain treated with?
opioids
Describe deep pain,
deep ACHING pain, felt as deep to the body surface, poorly localized
What is deep pain initiated by?
major trauma (postop pain, injury, or childbirth)
What does neuropathic pain result from?
nerve injury or infection
TRUE or FALSE: neuropathic pain is normally treated with opioids
FALSE: neuropathic pain responds POORLY to opioids
What is used to treat neuropathic pain?
antidepressants, cannabinoids, anticonvulsant
Which anticonvulsants can be used to treat neuropathic pain?
pregabalin and gabapentin
Is neuropathic pain stimulus dependent?
no, it is spontaneous and stimulus-independent
What is neuropathic pain characterized by?
allodynia, hyperalgesia, causalgia, and spontaneous (stimulus-independent) pain
classify the following as good or bad pain:
- musculoskeletal pain
- deep pain
- neuropathic pain
good pain: musculoskeletal and deep
bad pain: neuropathic
Which afferent fibers are non-pain fibers?
A-alpha and A-beta
What is the level of myelination and condution for A-alpha and A-beta fibers?
myelinated; rapidly conducting
What kind of information is transmitted via A-alpha and A-beta fibers?
touch, pressure, muscle afferent information
What is the level of myelination and conduction for A-delta fibers? What kind of information is transmitted?
- thinly myelinated; slow conduction
- carry first pain
What kind of receptors are associated with A-delta fibers?
high-threshold mechanoreceptors (mechanical nociceptors)
Where do A-delta fibers terminate?
in spinal lamina I (marginal zone) and lamina II and lamina V
(lamina I, II, V)
What is the level of myelination and conduction in C fibers? What kind of information is transmitted?
- unmyelinated; very slow conduction
- carry second pain
What are the 2 main types of C fibers?
peptidergic and isolectin B4 Positive (IB4+)
What kind of receptors (and stimuli) are associated with peptidergic C fibers?
- high threshold mechanoreceptors (strong mechanical stimulation)
- polymodal nociceptors (noxious heat mechanical stimuli, chemical irritants)
What kind of receptors (and stimuli) are associated with IB4+ C fibers?
Low threshold mechanoreceptors (gentle mechanical stimulation)
Which type of fiber is known as a silent nociceptor?
IB4+ C fiber
Which NT do all sensory neurons use?
all use glutamate
Which NT do A beta fibers use?
Which NT do A delta fibers use?
Which NT do peptidergic C fibers use?
Which NT do non-peptidergic C fibers use?
A beta = glutamate
A delta = glutamate, sub P, CGRP
pep C = glutamate, sub P, CGRP
non-pep C = glutamate
Which afferent fiber is classified by the following:
- heavily myelinated
- fast conduction velocity
- large soma diameter
- transduce low threshold
- innocuous stimuli
A beta
Which afferent fiber is classified as the following:
- thinly myelinated
- medium conduction velocity
- medium soma diameter
- can transduce innocuous/noxious stimuli
A delta
Which afferent fiber is classified as the following:
- non-myelinated
- slow conduction velocity
- transduce noxious stimuli
peptidergic C
Which afferent fiber is classified as the following:
- non-myelinated
- slow conduction velocity
- small soma diameter
- transduce noxious stimuli
- binds IB4
- does not produce pro-nociceptive peptides (CGRP/SubP)
non-peptidergic C
Which receptor makes a cell/fiber peptidergic?
TrkA
What does the receptor TrkA bind?
NGF (nerve growth factor) - keeps cell alive by nociceptor
TRUE or FALSE: peptidergic C fibers depend on NGF for survival and function, whereas non-peptidergic C fibers depedns on GDNF
TRUE
Where do pain fibers project to in the spinal cord? Which horn?
- lamina II (substantia gelatinosa)
- lamina I (marginal zone)
- lamina V
(dorsal horn)
Which lamina in the dorsal horn exclusively has pain-sensing cells (A delta, C)?
lamina I (marginal zone)
Which lamina in the dorsal horn has integrators of different sensory stimuli?
lamina V
Where do lamina I projection neurons project to?
- brainstem
- parabrachial nucleus
- hypothalamus
- thalamus
What kind of neurons are involved in local withdrawal and autonomic reflexes?
local circuit interneurons
Which laminae have dendrites of wide dynamic range?
IV and V
What kind of receptors does the glutamate released form afferent fibers bind to?
AMPA and NMDAR
Which receptor is responsible for faster first pain?
AMPAR
What act as modulators for pain signals in the dorsal horn?
- GABA/Gly interneurons
- substance P and CGRP
Which endogenous opioids can be released by some inhibitory INs?
enkephalin and endorphin
Which 2 NTs are mostly responsible for preventing pain?
5HT and NA
TRUE or FALSE: 5HT can be excitatory or inhibitory
TRUE
Where do descending pathways come from to release endogenous opioids?
rostroventral medulla (RVM)
Most axons of lamina I and lamina V projection neurons cross midline and ascend in the _______________ quadrant of the spinal cord.
anteriolateral
What are the 3 main pain tracts in the spinal cord?
- spinothalamic tract
- spinoreticular tract
- spinomesencephalic tract
TRUE or FALSE: the pain pathways cross over at the midbrain
FALSE: cross at spinal cord
TRUE or FALSE: the lateral division of the spinothalamic tract is phylogenetically old, whereas the medial division is recent
FALSE: lateral = recent; medial = old
What is another name for the medial and lateral divisions of the spinothalamic tract?
- medial = paleospinothalamic tract
- lateral = neospinothalamic tract
Where does the paleospinothalamic tract project to? neospinothalamic tract?
- paleo = intralaminar thalamic neurons –> association and prefrontal cortex
- neo = ventroposteriolateral (VPL) nucleus of the thalamus –> somatosensory cortex –> parietal lobe
Which division of the spinothalamic tract transmits affective and alerting aspects of pain?
medial/paleo
What kind of pain is the medial ST tract associated with? lateral?
- medial = slow (second) pain
- lateral = fast (first) pain
Which division of the ST tract lacks a somatotopic map? What does this imply about the pain you feel? Instead of a somatotopic map, what does this ST tract have?
- medial lacks map
- poorly localized pain
- large receptive fields from dorsal horn cells
TRUE or FALSE: The lateral division of the ST tract carries localized and discriminative aspects of pain
TRUE
What percentage of VPL neurons are nociceptive?
10%
TRUE or FALSE: the spinoreticular tract is topographically organized
FALSE: spinoreticular tract LACKS topographical organization
Where does the SR tract project to?
spinal cord –> reticular formation –> thalamus
Do reticular neurons have a wide or narrow receptive field?
wide (like paleoST tract dorsal horn cells)
What aspect of pain information does the SR tract carry?
general aspects of pain perception (e.g. ALERTS ONSET OF PAIN)
Where does the spinomesencephalic tract project to?
spinal cord –> midbrain PAG –> hypothalamus (lateral parabrachial area) –> NTS –> amygdala
What occurs in the PAG in terms of pain transmission? Which tract is this part of ?
- ascending pain signals interact with descending analgesic info from emotional centers (e.g. amygdala)
- SM tract
What kind of responses to pain does the hypothalamus, NTS, and amygdala deal with?
autonomic, affective, and neuroendocrine responses to pain
TRUE or FALSE: the lateral parabrachial area adds value to sensory information
FALSE: the amygdala
(note: lateral parabrachial area is part of the hypothalamus)
Which cortical structures are involved in pain processing?
- anterior cingulate cortex
- prefrontal cortex
- insular cortex
- somatosensory cortex
Which aspect of pain is the ACC responsible for?
attention
Which aspect of pain is the PFC responsible for?
decision-making/judging the stimulus
Which aspect of pain is the insular cortex responsible for?
emotional value in pain processing