Case 2 - Pathophysiology of Pain

Question 1

what are nociceptors

Answer 1

high threshold sensory neurones of the peripheral somatosensory nervous system capable of transuding a range of noxious stimuli

Question 2

what is the TRPV1 receptor activated by

Answer 2

noxious heat

Question 3

what is the TRPM8 receptor activated by

Answer 3

noxious cold

Question 4

what activates the TRPV1 channels

Answer 4

Capasicin - found in chilies

Question 5

what activates TRPM8

Answer 5

methanol

Question 6

what are ASIC channels activated by

Answer 6

protons

Question 7

what are the P2X/Y channels activated by

Answer 7

ATP

Question 8

what can peripheral nociceptor terminals be activated by

Answer 8

the painful stimulus directly or activation and release of stimulatory signals from neighbouring cells

Question 9

what may these neighbouring cells be

Answer 9

keratinocytes

Question 10

what do nociceptors release

Answer 10

they are glutamatergic and peptidergic so they release glutamate, substance P and CGPR

Question 11

where do the cell bodies of sensory neurones reside

Answer 11

within the dorsal root ganglia

Question 12

features on sensory neurones.

Answer 12

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

Question 13

what nociceptors are only activated under inflammatory conditions

Answer 13

the silent poly modal nociceptors

Question 14

what is sensitisation

Answer 14

increased responsiveness of nociceptive neurones to their normal input, and/or recruitment of a response to normally sub threshold inputs

Question 15

what also may occur

Answer 15

spontaneous discharges and increases in receptive field size may also occur.

Question 16

what is nociplastic pain

Answer 16

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

Question 17

how can we assess pain using a stimulus evoked approach

Answer 17

using Von Frey Filaments
Pain diaries

Question 18

what is the visual analogue scale approach

Answer 18

0-10 VAS numeric pain distress scale
Wong-Baker faces pain rating scale

Question 19

what are the earliest responders to the site of injury

Answer 19

mast cells

Question 20

what does injury induce

Answer 20

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

Question 21

what does this lead to

Answer 21

the perception that this area of tissue has been damaged

Question 22

what kind of stimulation of the afferent terminals can occur and what does it lead to

Answer 22

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

Question 23

what does this lead to

Answer 23

more activation of more afferents and suddenly a much larger area may be perceived as being quite painful

Question 24

what are the direct receptor mediated excitatory effects

Answer 24

histamine, TNF alspha release

Question 25

are histamine and TNF alpha long or short lasting

Answer 25

long lasting

Question 26

what is the first inflammatory cells

Answer 26

neutrophils are the first to infiltrate the damaged tissue, after mast cells

Question 27

what happens when there is a depletion of neutrophils

Answer 27

decreases thermal hyperalgesia

Question 28

what does the direct role of peripheral inflammatory mediators elicit

Answer 28

vascular permeability and increased cell recruitment

Question 29

describe sodium channels in insured sensory neurones

Answer 29

they are unregulated - increased excitability and ectopic firing

Question 30

what is paroxysmal extreme pain disorder caused by

Answer 30

the gain of function mutation in the Na1.7 voltage gated sodium channel

Question 31

what do rare mutations the Na1.7 gene cause

Answer 31

congenital insensitivity or indifference to pain

Question 32

what is used to treat trigeminal neuralgia

Answer 32

carbamazepine

Question 33

what is used to treat HIV sensory neuropathy and central post stroke pain

Answer 33

lamotrigine

Question 34

what is used to treat PHN

Answer 34

topical lidocaine

Question 35

what does increased c fibres activity lead to

Answer 35

• 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

Question 36

mechanism of NMDA receptors

Answer 36

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

Question 37

describe the a beta fibres

Answer 37

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

Question 38

what is allodynia normally just activated by

Answer 38

c fibres

Question 39

spinal sensitisation

Answer 39

have a facilitator of these spinal neurones so an input leads to this prolonged response of second order neurones, they start firing more

Question 40

inhibitory interneurones in the spinal cord

Answer 40

GABAergic and glycinergic

Question 41

inhibitory modulating pathways in the brain

Answer 41

descending inhibitory pathways originate in the anterior cingulate gyrus, amygdala and hypothalamus and are relayed to the spinal cord

Question 42

examples of brain inhibitory neurotransmitters

Answer 42

NA, 5-HT, opioids

Question 43

what does increasing a beta input do

Answer 43

gives pain relief by shutting the pain Gaye