pain and nociception

Question 1

congenital analgesia

Answer 1

mutations in number of SCN genes, codes for Nav1.7, 1.8 and 1.9 sodium channels found in nociceptive fibres

Question 2

nociception

Answer 2

sensory process that provides signals that trigger pain

Question 3

pain

Answer 3

feeling or perception of irritating, sore, stinging, aching, throbbing, miserable or unbearable sensations arising from a part of the body

Question 4

chronic pain

Answer 4

inflammatory pain, neuropathic pain, neuralgias, musculoskeletal pain, viceral, cancer

Question 5

anatomy and physiology of nociceptors

Answer 5

found in periphery as simple free nerve endings, peripheral nerve fibre branches and terminates naked, unmyelinated endings in dermis

Question 6

types of nociceptors

Answer 6

transduction of painful stimuli occurs in the free nerve endings of unmyelinated C fibres and thinly myelinated A delta fibres, some nociceptors only respond to one modality - mechanical; respond to strong pressure, thermal; respond to burning heat/ extreme cold, chemical; respond to histamine or other chemicals, most nociceptors are polymodal

Question 7

recording from nociceptive fibres

Answer 7

record afferent in response to incremental temperatures, graphs plotting afferent firing frequency vs temperature

Question 8

classification of sensory afferent innervating nociceptors

Answer 8

small diameter, slow conducting afferents associated with nociceptors and thermoreceptors, cell bodies of nociceptive afferents in Doral root ganglia are smaller

Question 9

first pain

Answer 9

fast A-delta fibres, sharp or prickling, easily localised, occurs rapidly, short duration, mechanical or thermal nociceptors

Question 10

second pain

Answer 10

slow C-fibres, dull ache/ burning, poorly localised, slow onset, persistent, polymodal nociceptors

Question 11

physiological basis of nociceptive pain

Answer 11

activation of peripheral nociceptors that express heterogenous populations of receptors/ion channels, transmission of impulses via A-delta and C- sensory afferents to the dorsal horn, projection to brain via ascending pathways, subjective experience of sensory and emotional components of pain

Question 12

spinal connections of nociceptive axon terminals

Answer 12

nociceptive fibres have their cell body within the Doral root ganglion, afferent terminals enter the dorsal horn and travel up/down a short distance within the zone of lissauer, afferent terminals synapse onto neurones (2nd order) within the superficial laminae of the Doral horn, principle areas innervated by nociceptive afferents are lamina 1 and lamina 2 (substantia gelatinosa)

Question 13

convergence of nociceptive inputs from the skin and viscera

Answer 13

noiceceptive afferents from internal organs and the skin enter spinal cord through common routes and target overlapping populations of spinal neurones, this cross-talk accounts for referred pain where by visceral pain is perceived as having a cutaneous source by the sufferer

Question 14

nociceptive afferent neurotransmitters

Answer 14

release glutamate, some fibres use neuropeptides such as substance P and CGRP

Question 15

ascending pain pathway

Answer 15

processes afferent inputs from peripheral mechano, thermal and polymodal nociceptors, contralateral pathway, information relayed to thalamus then to the somatosensory cortex, 3 components - lateral (Neo) spinothalamic (how intense is the pain, where is it localised) tract, spinoreticulothalamic tract (or paleospinothalamic)-pain motivation, affective and behavioural responses, anterior spinothalamic tract-crude touch and pressure

Question 16

spinoreticulothalamic tract

Answer 16

crosses at level of the spinal cord, some neurones project to the reticular formation of the medulla whilst other project into the reticular formation of the pons then onto the thalamus then to the somatosensory cortex

Question 17

spinal touch pathway vs spinal pain pathway

Answer 17

touch - crosses at level of medulla, pain - crosses at level of the spinal cord

Question 18

dissociated sensory loss

Answer 18

unilateral spinal cord injury - produce sensory loss of touch, pressure, vibration and proprioception below the lesion on the same side, diminished sensation of pain below the lesion observed on the opposite side, this is called dissociated sensory loss

Question 19

pain and temp pathway from the face and head - trigeminal system

Answer 19

5th cranial nerve, smaller diameter afferents depend in the spinal trigeminal tract to the brain stem, synapse with second order sensory neurones in pars caudalis, axons ascend contralaterally to thalamus in the trigeminothalamic tract (trigeminal lemniscus), projects to cortex via the ventral posteromedial nucleus, innervates specialised structures

Question 20

gender differences in extent of activation

Answer 20

positron emission tomography, repetitive noxious heat applied, comparison of males and females, potential mechanisms - oestrogen; promotes release of proinflammatory cytokines from mast cells, macrophages and T cells, testosterone; enhances production of anti-inflammatory cytokines by macrophages, sex hormones may mediate opioid actions in sex-specific mechanisms

Question 21

prolactin in female-selective hypersensitivity

Answer 21

PRLR-S = short - causes sensitisation, PRLR-L = long - normally inhibits but in some pain disorders this is down-regulated

Question 22

pain complex sensory experience

Answer 22

endogenous analgesia and pain modulation - sensory inputs without pain sensations, hyperalgesia - increased pain, allodynia - touch evoked pain, phantom pains - pain and touch sensations with no sensory inputs

Question 23

local peripheral chemical mediators of hyperalgesia

Answer 23

tissue damage and inflammation triggers release of substances (prostaglandins, bradykinin and histamine) that can sensitise peripheral nociceptors and induce hyperalgesia

Question 24

diminished inhibition contributes to central sensitisation

Answer 24

normal nociceptive neurotransmission subject to inhibitory controls, decreased GABA and glycine synthesis or loss of these inhibitory interneurones after nerve injury leads to disinhibition of A-delta and C inputs and increased excitability, this may contribute to hyperalgesia or cancer pain

Question 25

phantom pain

Answer 25

50-80% amputees, highly resistant to treatment, may be result of cortical reorganisation in the virtual body maps of thalamus and cortex, in phantom limb maps are distorted such that stroke on face felt on missing limb, targeted muscle reinnervation may reduce phantom limb pain as residual nerves from amputated nerves are transferred to reinnervate new muscle targets that have lost their function

Question 26

pain interpretation

Answer 26

can vary greatly from reality of painful stimulus - soldier suffering severe battle wounds but caring on fighting, labour pains vanish upon birth, sporting injuries, placebo effect of drugs, the perception of pain is subject to central modulation, distraction leads to lower perception of pain and decreased activity in the cortex

Question 27

opioids

Answer 27

modulate nociceptive transmission, opiate-like chemicals produced in the body that control pain, immune responses and other body function, delta opioid receptors located on excitatory interneurones in the dorsal horn, activation of these receptors inhibits these cells, reduced pain sensation

Question 28

endocannabinoids

Answer 28

endogenous ligands identified anandamide and 2-arachidonyl-glycerol, CB1 and CB2 receptors clones, acts at spinal and supra spinal sites

Question 29

sensory neurone specific channels

Answer 29

in subjects with congenital insensitivity to pain mutations in TrkA that bind nerve growth factor and important mediator of inflammatory pain