Week 6-8: Pain Flashcards
The cell bodies of the nociceptors (primary afferent neurons) are located in the
dorsal root ganglion
Primary afferent neurones synapse in the
dorsal horn
Thinly myelinated with conduction velocities between 5-30 m/s
Aδ-fibre axons
Unmyelinated with conduction velocities
C-fibre axons
Slow pain is induced by activation of which fibres
C-fibres
Fast pain is induced by activation of which fibres
Aδ-fibres
True or false:
TRPM8 channel is only a considered nociceptor in the cornea
True, it is a moderate stimulus receptor and thus usually not considered a nociceptor
True or false:
TRPM8 can also respond to changes in osmolarity
True
PGE2 increases the sensitivity of which channels to capsaicin and heat
TRPV1
Hyperalgesia
Refers to when a normally weakly-painful stimulus becomes more overtly painful
Allodynia
Refers to triggering of a pain response from stimuli which do not normally provoke pain
Sensitisation
A change in neuronal sensitivity that results in heightened pain being generated by normally weakly painful or non-painful (innoxious) stimuli, e.g. sunburn - induces pain and heightened sensitivity to thermal stimuli.
Occurs due to a change in the sensitivity of nociceptors so that their threshold for activation is reduced
Peripheral sensitisation and inflammation mechanism
Activation of ‘peptidergic’ nociceptors contributes to the inflammatory response (neurogenic inflammation)
A sub-population of C-fibre nociceptors contain and release calcitonin gene-related peptide (CGRP) causing vasodilation as well as substance P that activates mast cells to release histamine and cause vascular leakage (leading to oedema). This leads to the release of H+, prostaglandins, bradykinin, 5HT, ATP, NGF. The nerve terminals of nociceptors express receptors for these substances and their activation leads to a reduction in the nociceptor threshold for activation - i.e. sensitisation.
PGE2 increases the sensitivity of a) ____ channels to b) _____
a) TRPV1
b) capsaicin and heat
Maintenance of peripheral sensitisation
NGF (as an example) activates its receptor and is internalised together with its receptor and transported back into the cell body in the dorsal root ganglion.
This can induce an increase in gene transcription and translation in the cell body leading to increase in receptors (e.g. TRPV1, bradykinin) and ion channels (Na+ channels). These changes contribute to the maintaining the reduced threshold of nociceptors; increasing receptor number lowers the threshold for activation, increasing Na+ channel number increases likelihood of generating AP.
C-fibres terminate in which layers of the dorsal horn?
1 and 2
Aδ fibres usually terminate in which laminas of the dorsal horn?
1 and 5
Wind-up
Wind-up is generated by repeated activation of C-fibre nociceptors leading to a progressive increase in perceived pain (i.e. the same stimulus generates more pain); requires high frequency input arrives at more than 1 impulse every 3 seconds.
* Response to Aδ-fibre inputs remains unchanged.
Characteristic of wide-dynamic-range neurons - affected the most.
SHORT-TERM sensitisation of dorsal horn neurons.
Same stimulus generates more pain - doesn’t lower threshold of activation but generates greater activity for same stimulus
TRUE OR FALSE:
wind-up sensitization lowers threshold for activation and thus leads to increased pain.
False, generates greater activity for the same stimulus rather than lowering threshold.
Erythromyalgia
Two gain of function mutations in Nav1.8 voltage-gated sodium channel gene leads to decreased threshold for channel and increased excitability of nociceptor
PRDM12 mutations cause
affects development of certain types of sensory neurons - leads to congenital pain insensitivity
Classification of ‘chronic’ pain
Regular pain experienced for 3 months or longer
NGF/TrkA mutations cause
Involved in maturation and differentiation of sensory neurons
Trigenimal neuralgia
Pain associated with territories innervated by sensory parts of trigenimal nerve - e.g. jaw
