Case 2 - Pathophysiology of Pain Flashcards
what are nociceptors
high threshold sensory neurones of the peripheral somatosensory nervous system capable of transuding a range of noxious stimuli
what is the TRPV1 receptor activated by
noxious heat
what is the TRPM8 receptor activated by
noxious cold
what activates the TRPV1 channels
Capasicin - found in chilies
what activates TRPM8
methanol
what are ASIC channels activated by
protons
what are the P2X/Y channels activated by
ATP
what can peripheral nociceptor terminals be activated by
the painful stimulus directly or activation and release of stimulatory signals from neighbouring cells
what may these neighbouring cells be
keratinocytes
what do nociceptors release
they are glutamatergic and peptidergic so they release glutamate, substance P and CGPR
where do the cell bodies of sensory neurones reside
within the dorsal root ganglia
features on sensory neurones.
they are pseudo unipolar which means that they out one axon which branches into two, and one branch goes centrally to the spinal cord and one goes peripherally out to innervate their target tissues e.g the skin
what nociceptors are only activated under inflammatory conditions
the silent poly modal nociceptors
what is sensitisation
increased responsiveness of nociceptive neurones to their normal input, and/or recruitment of a response to normally sub threshold inputs
what also may occur
spontaneous discharges and increases in receptive field size may also occur.
what is nociplastic pain
pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease
how can we assess pain using a stimulus evoked approach
using Von Frey Filaments
Pain diaries
what is the visual analogue scale approach
0-10 VAS numeric pain distress scale
Wong-Baker faces pain rating scale
what are the earliest responders to the site of injury
mast cells
what does injury induce
a mast cell degranulation process response releasing histamine and cytokines which are Able to stimulate receptors on primary sensory afferent terminals to generate an action potential
what does this lead to
the perception that this area of tissue has been damaged
what kind of stimulation of the afferent terminals can occur and what does it lead to
antidromic stimulation of afferent terminals can occur which will lead to release of neuropeptides from these afferent terminals and these are able to bind to receptors on mast cells and induce more degranulation, release of histamines and different cytokines
what does this lead to
more activation of more afferents and suddenly a much larger area may be perceived as being quite painful
what are the direct receptor mediated excitatory effects
histamine, TNF alspha release
are histamine and TNF alpha long or short lasting
long lasting
what is the first inflammatory cells
neutrophils are the first to infiltrate the damaged tissue, after mast cells
what happens when there is a depletion of neutrophils
decreases thermal hyperalgesia
what does the direct role of peripheral inflammatory mediators elicit
vascular permeability and increased cell recruitment
describe sodium channels in insured sensory neurones
they are unregulated - increased excitability and ectopic firing
what is paroxysmal extreme pain disorder caused by
the gain of function mutation in the Na1.7 voltage gated sodium channel
what do rare mutations the Na1.7 gene cause
congenital insensitivity or indifference to pain
what is used to treat trigeminal neuralgia
carbamazepine
what is used to treat HIV sensory neuropathy and central post stroke pain
lamotrigine
what is used to treat PHN
topical lidocaine
what does increased c fibres activity lead to
- increased glutamate release as an excitatory amino acid and also substance P
- sustained glutamate processing is able to initiate secondary changes in spinal processing such as activation of NMDA receptors
mechanism of NMDA receptors
they are glutamate receptors that normally have a magnesium block residing within them so they are normally not active but when levels of glutamate increase, so much that the magnesium kick can be overcome, thus can lead to activation of these post synaptic NMDA receptors and activation of second order neurones
describe the a beta fibres
low threshold mechanoreceptors that are activated by low threshold touch.
these can converge on the same neuronal circuit either directed through synaptic reorganisation branches or indirectly though interneurones
what is allodynia normally just activated by
c fibres
spinal sensitisation
have a facilitator of these spinal neurones so an input leads to this prolonged response of second order neurones, they start firing more
inhibitory interneurones in the spinal cord
GABAergic and glycinergic
inhibitory modulating pathways in the brain
descending inhibitory pathways originate in the anterior cingulate gyrus, amygdala and hypothalamus and are relayed to the spinal cord
examples of brain inhibitory neurotransmitters
NA, 5-HT, opioids
what does increasing a beta input do
gives pain relief by shutting the pain Gaye
