Physiology Pain Flashcards
what is pain
unpleasant sensory and emotional experience, associated with actual tissue damage or described in terms of such damage
what is nocieptive pain
adaptive- an immediate protective response, short lived
what is inflammatory pain
adaptive- assists healing, persists over days, possibly weeks
what is pathological pain
maladaptive- no physiological purpose, persists over months, years, lifetime
how is acute mild pain managed
NSAIDs, paracetamol (doesnt resolve inflammation), opiods (in moderate/ severe cases)
what types of drug manage chronic pain
antidepressants
anticonvulsants
local anaesthetics
what are nociceptors
specific peripheral sensory afferent neurones normally activated preferentially by intense stimuli that are noxious
where are the central terminals on nociceptors
in CNS
what transmitter does nociceptors release
glutamate
what is the peripheral end of a nociceptor like
free nerve ending
what are the two types of nociceptor and what do they do
Adelta- are mechanical/thermal nociceptors that are thinly myelinated, respond to noxious mechanical and thermal stimuli. Mediate ‘first’, or fast, pain
C fibres- unmyelinated, collectively respond to all noxious stimuli (e.g. they are polymodal). Mediate ‘second’, or slow, pain (burning, throbbing, cramping, aching)
what causes secondary pain
Secondary pain results from a developing inflammation response- the chemicals in this inflammation activate the C fibres
what happens when a stimuli activates a nociceptor nerve ending
Na/Ca2+ influx
depolarised membrane
volatge gates Na+ channel activation
action potential to CNS
what are the thermal stimuli receptors
transient receptor potential A1, C3, V1
when is TRPV1 sensitised
in inflammation- means in is active at body temperature
what is the receptors for a noxious chemical stimuli
H+ activates acid sensing ion channels (ASICs), ATP activates P2X and P2Y receptors, bradykinin activates B2 receptors
what is the difference between the two types of Adelta fibres
type I and II
type I activates at a higher temp than type II
where is the soma of a nociceptor
within dorsal root ganglion (or trigeminal ganglion)
what is the nociceptive pathway in the spinal cord
enter dorsal horn
cross segmentally
ascend in spinothalamic or spinoreticulithalamic tracts
Peptidergic polymodal nociceptors are a type of C fibre, what is their function
have afferent and efferent functions:
-afferent: transmit nociceptive info to CNS via release of glutamate and peptides (substance P and neurokini A) within dorsal horn
-efferent: release pro inflam mediators (CGRP, substance P) from peripheral terminal which contributes to neurogenic inflammation
what can long term noxious stimulation cause
increased spinal excitability= hyperalgesia, allodynia (pain when no stimuli)
what do glutamate and peptides do
glutamate= mediates fast synaptic response peptides= mediates slow synaptic response
what is released from free nerve ending of peptidergic nociceptor due to tissue damage, or inflammatory mediators
peptides: substance P and CGRP
what does substance P cause
(i) local vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins)
(ii) release of histamine from mast cells
(iii) sensitizes surrounding nociceptors
what does CGRP cause
induces vasodilation
what is the end result of neurogenic inflammation
Primary and secondary hyperalgesia and allodynia
how does neurotransmission occur between the primary afferent and second order neurones in the dorsal horn
Action potential arrives at central terminal and opens ca channels, calcium influx, exocytosis, glutamate release
Glutamate diffuses across synaptic cleft and causes a fast excitatory postsynaptic potential
Activates glutamate receptors (primarily postsynaptic AMPA receptors with NMDA receptor participation (when afferent input is intense) )
(Normally NDMA receptors are silent as usually blocked by magnesium ion (pos charge). When the cells become depolarised by AMPA then magnesium pops out as membrane becomes more negative and the receptor can then contribute to transmission)
Peptides (substance P and CGRP) also participate (particularly during high frequency stimulation) causing a slow and prolonged e.p.s.p. that facilitates activation of NMDA receptors by relieving voltage-dependent block by Mg2+
sensitivity of post synaptic cell to glutamate is increase
where are the cell bodies of the primary afferent neurones
dorsal root ganglia
where do axons from the primary afferent cell bodies terminate
in dorsal horn of spinal cord in various laminae of rexed
C and A delta fibres terminate superficially in laminae I and II
what do nociceptive specific cells synapse with
only C and Asimga fibres
what cells receive input from Abeta fibres
proprioceptive
what do wide dynamic range neurones receive input from
all three types of pain fibres and thus a wide range of stimuli (Abeta, A delta and C)
what does visceral arise from and what causes it
nociceptors covering tissues (e.g. peritoneum, pleura), or walls of hollow organs.
Originates from stretching, twisting, inflammation and ischaemia – but not cutting, or burning
what does visceral pain feel like
poorly localised, dull, aching, throbbing character
perceived at a distance from the affected organ
associated with autonomic features (sweating, nausea, vomiting, pallor)
what is the path of visceral afferents from nociceptors
follow sympathetic pathways before entering the dorsal horn
what causes referred pain
some visceral and skin afferents converge upon the same spinothalamic neurones (all cells with a visceral receptive field also have a separate cutaneous RF)
The brain ‘interprets’ the nociceptive information arising from the viscera as originating from an area of skin that may be distant to the internal organ
where do terminals of visceral nociceptors terminate
in laminae I and V not II
what can happen to the segemental dermatome in referred pain
may show signs of hyperalgesia
what is the segmental dermatome for the heart
T1-5
what is the segmental dermatome for the gallbladder
C4
what does viscerosomatic pain feel like
sharp and well localised
what causes viscerosomatic pain
when inflammatory exudate from a diseased organ contacts a somatic (body wall) structure (e.g. parietal peritoneum)
where is referred gall bladder pain
shoulder
where is referred diaphragm pain
shoulder
where is referred liver pain
neck
where is stomach/ pancreas referred pain
centre of chest below nipple line
where is the REFERRED pain from appendix felt
umbilicus
are pain and nociception the same thing
no can have pain with no nociception
pain is awareness of suffering
what is the gate control theory
Pain evoked by activity in nociceptors (C- and Aδ- fibres) can be reduced by simultaneous activity in low threshold mechanoreceptors (Aβ-fibres)
Innocuous and nociceptive signals conduct to the spinal cord via Aβ- and C/Aδ- fibres respectively and are in part processed by neuronal circuits of the …?
substantia gelatinosa
what allows the gate control theory to work
Certain projection neurones (P) within the substantial gelatinosa project to the spinothalamic tract and are postulated to be excited by both large diameter (Aβ) sensory axons and unmyelinated (C/Aδ) nociceptive axons
The projection neurone (P) inputs are inhibited by an interneurone (I) and the interneurone is excited by the large sensory axon and inhibited by the nociceptive axon
Thus, activity in the nociceptive axon alone maximally excites the projection neurone, allowing nociceptive signals to arise to the brain
what are the two major ascending nociceptive tracts
spinothalamic tract
spinoreticular tract
where do projection neurones from lamina I (fast fibre Adelta pain) terminate
posterior nucleus of the thalamus
where do projection neurones from lamina V (WDR neurones) terminate
in the posterior ventroposterior nucleus of the thalamus
what does the spinoreticular tract mainly transmit
slow C fibre pain
what does the spinoreticular tract connect with in the brain
reticular nuclei in brain stem and parabrachial nucleus
what does the spinoreticular tract do
autonomic response to pain, arousal, emotional responses, fear of pain
what in the spinothalamic needs to BOTH be stimulated in order to feel pain
fibres in lamina 1 (delta) and 5 (WDR neurones)
are all thermoreceptors the same
no have warm and cold sensitive neurones
