Week 6-8: Pain

Question 1

The cell bodies of the nociceptors (primary afferent neurons) are located in the

Answer 1

dorsal root ganglion

Question 2

Primary afferent neurones synapse in the

Answer 2

dorsal horn

Question 3

Thinly myelinated with conduction velocities between 5-30 m/s

Answer 3

Aδ-fibre axons

Question 4

Unmyelinated with conduction velocities

Answer 4

C-fibre axons

Question 5

Slow pain is induced by activation of which fibres

Answer 5

C-fibres

Question 6

Fast pain is induced by activation of which fibres

Answer 6

Aδ-fibres

Question 7

True or false:

TRPM8 channel is only a considered nociceptor in the cornea

Answer 7

True, it is a moderate stimulus receptor and thus usually not considered a nociceptor

Question 8

True or false:

TRPM8 can also respond to changes in osmolarity

Answer 8

True

Question 9

PGE2 increases the sensitivity of which channels to capsaicin and heat

Answer 9

TRPV1

Question 10

Hyperalgesia

Answer 10

Refers to when a normally weakly-painful stimulus becomes more overtly painful

Question 11

Allodynia

Answer 11

Refers to triggering of a pain response from stimuli which do not normally provoke pain

Question 12

Sensitisation

Answer 12

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

Question 13

Peripheral sensitisation and inflammation mechanism

Answer 13

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.

Question 14

PGE2 increases the sensitivity of a) ____ channels to b) _____

Answer 14

a) TRPV1

b) capsaicin and heat

Question 15

Maintenance of peripheral sensitisation

Answer 15

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.

Question 16

C-fibres terminate in which layers of the dorsal horn?

Answer 16

1 and 2

Question 17

Aδ fibres usually terminate in which laminas of the dorsal horn?

Answer 17

1 and 5

Question 18

Wind-up

Answer 18

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

Question 19

TRUE OR FALSE:

wind-up sensitization lowers threshold for activation and thus leads to increased pain.

Answer 19

False, generates greater activity for the same stimulus rather than lowering threshold.

Question 20

Erythromyalgia

Answer 20

Two gain of function mutations in Nav1.8 voltage-gated sodium channel gene leads to decreased threshold for channel and increased excitability of nociceptor

Question 21

PRDM12 mutations cause

Answer 21

affects development of certain types of sensory neurons - leads to congenital pain insensitivity

Question 22

Classification of ‘chronic’ pain

Answer 22

Regular pain experienced for 3 months or longer

Question 23

NGF/TrkA mutations cause

Answer 23

Involved in maturation and differentiation of sensory neurons

Question 24

Trigenimal neuralgia

Answer 24

Pain associated with territories innervated by sensory parts of trigenimal nerve - e.g. jaw