Neurology Of Pain

Question 1

What are the 4 types of nociceptors

Answer 1

Thermal (a or c fibre)
Mechanical (a fibre)
Chemical (c fibre)
Polymodal

Question 2

Example of thermal nociceptor and how it is activated

Answer 2

Capsaicin receptor: heat ctiavted ion channel in the pain pathway
Capsaicin elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the CNS
Receptor is a non-selective cation channel that is structurally related to TRP family of ion channels

Question 3

Alliums activate what channel and temperature range

Answer 3

TRPA1
Up to 17 degrees

Question 4

Menthol activates what pathway

Answer 4

TRPM8
8-28 degrees

Question 5

Swell activates… pathway

Answer 5

TRPV4
Above 27 degrees

Question 6

Extreme heat is what pathway?

Answer 6

TRPV2
Above 52 degrees

Question 7

Capsaicin activates what pathway

Answer 7

TRPV1
Above 43

Question 8

Camphor activates what pathway

Answer 8

TRPV3
Above 31 or 39 degrees

Question 9

Examples of mechanism-sensitive TRP channels

Answer 9

TRPV1, 2 and 4

Question 10

Describe the process of nociception

Answer 10

Noxious stimuli (transduction)
Conduction Primary sensory neuron
Transmission and modulation in central neuron
Unipolar conduction of pain
There is also pseudo-unipolar conduction of pain
Release of neuropeptides important in the immune response to pain

Question 11

Acute pain is…

Answer 11

Physiological

Question 12

Chronic pain is…

Answer 12

Pathological

Question 13

Nociception and inflammatory pain

Answer 13

Sudden onset in response to a discrete event
Recedes during healing

Question 14

Neuropathic pain overview

Answer 14

Persists long after recovery (>3 months)
Often difficult to tie to a specific event
Often unresponsive to analgesics

Question 15

how is neuropathic pain caused

Answer 15

Occurs as a result of a lesion or disease in the P/CNS – change in neurone not the tissue
Eg diabetic neuropathy, multiple sclerosis, fibromyalgia or spinal cord injury
Can present as burning or tickling or dull aches
May be associated with allodynia or hyperalgesia
Due to sensitisation of peripheral and central neurons
Peripheral sensitisation - increased sensitivity of C and A fires due to prostaglandin release, increased voltage dependent na+ channel expression

Question 16

What s hyperalgesia

Answer 16

Increased intensity of pain sensation for a given nociceptive stimulus

Question 17

What is allodynia

Answer 17

Sensation of pain in response to something not normally painful in nature eg light touch near a wound

Question 18

How could the increased Na channels cause an increase in nociceptor sensitivity?

Answer 18

Increase likelihood that the threshold will be reached
Peripheral sensitisation - increased Na channels and increased nociceptor sensitivity

Question 19

What is central sensitisation

Answer 19

Glutamate/NMDA receptor mediated sensitisation
Increased glutamate release because of peripheral sensitisation
Increased expression of glutamate receptors (windup phenomenon)
Hyperalgesia

Question 20

Disinhibition by central sensitisation

Answer 20

Normally GABA release modulates pain transmission
In injury this inhibition can be lost - hyperalgesia
Disinhibition can allow A beta fibres to signal to DHNs - touch becomes painful - allogynia

Question 21

Microglial cell activation by central sensitisation

Answer 21

Cytokine release eg TNF alpha, IL-1b, IL-6
Persistent pain

Question 22

Describe phantom limb pain (peripheral mechanism)

Answer 22

Peripheral mechanism
Proximal portion of the severed nerve sprout form neuromas
Increased Na+ channel expression
Hyperexcitability and spontaneous discharges
Doesn’t explain PLP in congenital absence of limbs

Question 23

Describe the central neural mechanisms of phantom limb pain

Answer 23

Spinal cord sensitisation and retiring of other sensory nerves onto DHNs
Windup phenomenon
Cortical reorganisation and cortical-motor sensory dissociation