Anatomy and Physiology of Pain Flashcards
4 processes of pain signalling
transduction
transmission
perception
modulation
transduction of pain
noxious stimuli translated into electrical activity at sensory nerve endings
transmission of pain
propagation of impulses along pain pathways
how many neurones of the pain pathway
3
what do nociceptors detect
tissue damage
which organ has no nociceptors
brain
what activates TRPV1 channels
heat, acid, capsaicin, mustard, wasabi
what activates TRPM8 channels
cold, menthol
what activates ASIC channels
h+ - Acid Sensing Ion Channel
what family of channels are important in temperature nociception
TRP family
what happens when a nociceptor is activated
signals sent along primary afferent sensory neurone
what effects speed of transmission along a neurone
myelination
axon diameter
which axon types carry ‘1st pain’ and ‘2nd pain’
1st - A delta
2nd - C
what are remak bundles
clusters of C fibres
what are NaVs and how many subtypes are there
voltage gated sodium channels
9
which NaV is heavily implicated in pain transmission
NaV1.7
what conditions are caused by gain of function and loss of function mutations in NaV1.7 channels
gain - inherited erythromelalgia
loss - congenital insensitivity to pain
congenital insensitivity to pain
rare condition where patient cannot feel pain
inherited erythromelalgia
neuropathy causing severe chronic burning pain in hands and feet
risks of congenital insensitivity to pain
wounds, broken bones, and health issues not detected
bone breaks heal badly as not treated
babies chew fingers, lips, tongue, etc
congenital insensitivity to pain with anhidrosis
inability to feel pain and temperature, and decreased or absent sweating
what causes congenital insensitivity to pain with anhidrosis
TRKA gene mutation -> decreased nerve growth factor -> decr A delta and C fibres
what causes diabetic neuropathy and where are effects most common
high or fluctuating blood glucose damage nerves
legs and feet
how many laminae in the dorsal horn, and entire spinal cord
5 in dorsal horn
10 across whole cord
which laminae of the dorsal horn do A delta nociceptor axons synapse to and what NT is released
lamina I
glutamate
what cells do C fibre nociceptor axons synapse to to indirectly activate lamina I cells
lamina II interneurons
what is caused when lamina II interneurons become spontaneously active
neuropathic pain
what part of the spinal cord do axons of projection neurons decussate in
anterior white commissure
projection neuron
second order neurones with cell body in dorsal horn
2 major ascending pathways carrying sensory info to the brain
spinothalamic tract
DCML
2 sub tracts within the spinothalamic tract
anterior spinothalamic
lateral spinothalamic
which spinothalamic tract mainly conducts crude light touch and pressure
anterior spinothalamic
which axon types give inputs to the anterior spinothalamic tract
A beta
A delta
C
where do 2nd order neurones in the anterior spinothalamic tract synapse to 3rd order neurones
thalamus - ventral posterior lateral and ventral posterior inferior nuclei
what information do 3rd order neurones in the anterior spinothalamic tract convey to the somatosensory cortex
exact localisation and physical intensity of noxious stimulus
which spinothalamic tract mainly conveys pain and temperature
lateral spinothalamic tract
which axon types input to the lateral spinothalamic tract
A delta
C
where do 2nd order neurones in the lateral spinothalamic tract synapse to 3rd order neurones
thalamus - mediodorsal, ventral posterolateral, and ventral posterior inferior nuclei
which parts of the cortex does the anterior spinothalamic tract innervate
primary and secondary somatosensory cortices
which parts of the cortex does the lateral spinothalamic tract innervate
anterior cingulate and rostral insular cortex
which spinothalamic tract also synapses to the limbic system, intralaminar nuclei of the thalamus, periaqueductal grey, and reticular formation other than the thalamus
lateral spinothalamic
role of the limbic system, intralaminar nuclei of the thalamus, periaqueductal grey, and reticular formation in pain perception
limbic - subjective sensations of pain and pleasure
INoT - arousal and desc control of nociceptor input
PAG - desc pain modulation
RF - alterting cerebral cortex and focus attention on pain
which brain region is responsible for the unpleasant nature of pain
limbic system
which spinothalamic tract controls sensory-discriminative/intensity of pain and which controls affective motivational/unpleasantness of pain
sens-disc anterior spinothalamic
aff-mot lateral spinothalamic
brain areas activated by pain
somatosensory cortex
cingulate cortex
amygdala
insula
what part of pain perception is controlled by the anterior cingulate cortex
emotional reaction
what part of pain perception is controlled by the pre frontal cortex
evaluation and cognition
what part of pain perception is controlled by the insula
pain mapping, interoception, homeostatic adjustment, emotion
what part of pain perception is controlled by the primary somatosensory cortex
location and intensity
what part of pain perception is controlled by the amygdala
aversion, emotional memory and response
3 major brain regions in pain modulation
peri aqueductal grey
locus coeruleus
raphe nucleus
role of descending inhibitory system to modulate pain
intrinsic analgesic response to prevent continuous pain
where is the periaqueductal grey and what effect is caused by its stimulation
around cerebral aqueduct in brainstem
analgesia
Natural methods of pain modulation
lamina II inhibitory neurons
endogenous opioids
A beta afferents
how are lamina II inhibitory neurons activated to modulate pain
axons descending spinal cord activate lamina II inhibitory interneurons -> release serotonin and noradrenaline -> inhib neurone activation
role of lamina II inhibitory neurones
block/dampen incoming nociceptive signals by releasing GAB and enkephalins which bind to A delta axons and lamina I dendrites
endogenous opioids
endorphins
enkephalins
dynorphins
3 opioid receptors
mu
delta
kappa
what cells release endogenous opioids
interneurons
how does opioid receptor activation reduce nociceptive transmission
decrease excitation at dorsal horn
why do people often not immediately feel pain after severe trauma
massive enkephalin release
how can activation of A beta fibres dampen pain
overwhelm secondary afferent neurons inhibiting nociceptive signal transmission
can synapse on lamina inhibitory neurones
how can activation of A beta fibres dampen pain
overwhelm secondary afferent neurons inhibiting nociceptive signal transmission
can synapse on lamina II inhibitory neurones
how does rubbing area reduce pain
activation of A beta afferents
how long does chronic pain last
over 3 months
allodynia
sensitised state where pain is caused by a non noxious stimulus
hyperalgesia
abnormal increased pain sensitivity is caused by a noxious stimulus
peripheral sensitisation
increased sensitivity to an afferent nerve stimuli at the peripheral site
central sensitisation
increased sensitisation to an afferent nerve stimuli at the CNS site
what causes peripheral sensitisation
Sensitisation of sensory primary afferent fibres
inflammatory mediators stimulate nocioceptive and up regulate ion channels in sensory fibres increasing membrane potential closer to depolarisation threshold
what causes central sensitisation
Sensitisation of projection neurones
continuous activation of projection neurones upregulates ion channels increasing depolarisation closer to threshold
2 types of peripheral sensitisation
ectopic activity
ephatic transmission
where can collateral sprouting induced pain occur
dorsal horn
what does Braak staging asses
distribution of Tau tangles in brain
what are Tau tangles made up of
hyperphosphorylated Tau
normal function of Tau
stabilises microtubules
how does hyperphosphorylation of Tau cause neurone death
microtubules not stabilised -> decr axonal support -> neurone fdeath
what gene encodes Tau
MAPT
how does level of beta amyloid and Tau in the CSF change in dementia
beta amyloid decr
Tau incr
why does CSF beta amyloid decrease in dementia -amyloid sink hypothesis
amyloid deposited in brain so not in CSF
how can dementia brain changes be assessed
MRI
how long before symptoms arise do pathological changes start to occur in dementia
~20 years