pain and nociception Flashcards
congenital analgesia
mutations in number of SCN genes, codes for Nav1.7, 1.8 and 1.9 sodium channels found in nociceptive fibres
nociception
sensory process that provides signals that trigger pain
pain
feeling or perception of irritating, sore, stinging, aching, throbbing, miserable or unbearable sensations arising from a part of the body
chronic pain
inflammatory pain, neuropathic pain, neuralgias, musculoskeletal pain, viceral, cancer
anatomy and physiology of nociceptors
found in periphery as simple free nerve endings, peripheral nerve fibre branches and terminates naked, unmyelinated endings in dermis
types of nociceptors
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
recording from nociceptive fibres
record afferent in response to incremental temperatures, graphs plotting afferent firing frequency vs temperature
classification of sensory afferent innervating nociceptors
small diameter, slow conducting afferents associated with nociceptors and thermoreceptors, cell bodies of nociceptive afferents in Doral root ganglia are smaller
first pain
fast A-delta fibres, sharp or prickling, easily localised, occurs rapidly, short duration, mechanical or thermal nociceptors
second pain
slow C-fibres, dull ache/ burning, poorly localised, slow onset, persistent, polymodal nociceptors
physiological basis of nociceptive pain
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
spinal connections of nociceptive axon terminals
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)
convergence of nociceptive inputs from the skin and viscera
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
nociceptive afferent neurotransmitters
release glutamate, some fibres use neuropeptides such as substance P and CGRP
ascending pain pathway
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
spinoreticulothalamic tract
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
spinal touch pathway vs spinal pain pathway
touch - crosses at level of medulla, pain - crosses at level of the spinal cord
dissociated sensory loss
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
pain and temp pathway from the face and head - trigeminal system
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
gender differences in extent of activation
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
prolactin in female-selective hypersensitivity
PRLR-S = short - causes sensitisation, PRLR-L = long - normally inhibits but in some pain disorders this is down-regulated
pain complex sensory experience
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
local peripheral chemical mediators of hyperalgesia
tissue damage and inflammation triggers release of substances (prostaglandins, bradykinin and histamine) that can sensitise peripheral nociceptors and induce hyperalgesia
diminished inhibition contributes to central sensitisation
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
phantom pain
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
pain interpretation
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
opioids
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
endocannabinoids
endogenous ligands identified anandamide and 2-arachidonyl-glycerol, CB1 and CB2 receptors clones, acts at spinal and supra spinal sites
sensory neurone specific channels
in subjects with congenital insensitivity to pain mutations in TrkA that bind nerve growth factor and important mediator of inflammatory pain
