Pain and Thermosensation Flashcards
What is pain?
An unpleasant sensory and emotional experience, associated with actual tissue damage or described in terms of such damage
What are the 3 forms of pain?
Nociceptive (acute) pain
Inflammatory (prolonged) pain
Pathological (neurogenic) pain
What are nociceptors?
Specific peripheral primary sensory afferent neurones normally activated preferentially by intense stimuli that are noxious or damaging
Where are nociceptor cell bodies located?
In the DRG and trigeminal ganglia (TG)
What order of neurone are nociceptors?
First order that relay information to second order neurones in the CNS by chemical synaptic transmission
What makes up nociceptors?
Aδ- and C-fibres
Where does nociceptor transduction begin?
Free nerve endings- mediated by numerous receptors and channels
What are Aδ fibres?
Mechanical/thermal nociceptors that are thinly myelinated-respond to noxious mechanical and thermal stimuli. Mediate first/fast pain
What are C-fibres?
Nociceptors that are unmyelinated- collectively they respond to all noxious stimuli (polymodal). Mediate second/slow pain
What is frequency coding?
The rate of AP discharge correlates with the intensity of the applied stimulus
What are the two types of Aδ- fibres?
Type I (HTM: high threshold mechanoreceptors) Type II
Describe type I Aδ- fibres?
Require strong mechanical stimuli for activation, activated by noxious head (>53’C).
Show sensitisation for a prolonged stimuli.
Threshold falls in setting of tissue injury, mediates first pain to intense mechanical stimuli
Describe type II Aδ- fibres?
Respond to noxious mechanical stimuli and also to noxious heat (43-47’C), sensitive to capsaicin.
Shows adaptation
Mediates first pain to heat
What are the sub-types of C-fibres (H=heat, M=mechano)?
C-MH
C-M
C-H
C-MiHi (silent)
Describe C-MH fibres
Respond to noxious mechanical stimuli, activated by noxious heat (39-51’C)
Sensitive to capsaicin
Shows sensitisation to repeated stimuli
Contributes to heat pain and stimulus location
Describe C-M fibres
Responds to noxious mechanical stimuli
Insensitive to heat and capsaicin
Describe C-H fibres
Respond to noxious heat (42-48’C)
Normally insensitive to mechanical stimuli, sensitive to capsaicin
Mediates heat hyperalgesia, does not contribute to precise localisation of stimulus
Acquires sensitivity to mechanical stimulation in the context of inflammation
Describe C-MiHi (silent) fibres
Normally insensitive to both mechanical and heat stimuli but acquires sensitivity following sensitisation by inflammatory mediators
Sensitive to capsaicin and other algesic or pro-algesic substances
What direction nociceptor signalling?
Bidirectional (e.g. peptidergic C-fibres)
Describe the central terminal of the nociceptor
Not responsive to environmental stimuli
Site of Ca2+ dependent transmitter release
Targeted by endogenous molecules that regulate activity
Describe the peripheral terminal of nociceptors
Responsive to environmental stimuli
Site of release of molecules that influence local tissue environment (sub P causes vasodilation and extravasation of plasma proteins, calcitonin gene related peptide causes vasodilation)
Targeted by endogenous molecules that regulate sensitivity
Where do nociceptor axons terminate?
Centrally in the orsal horn of the spinal cord in various laminae of Rexed (I-V)
Where do nociceptive C and Aδ-fibres mostly terminate?
Superficially in laminae I and II (also V for Aδ-fibres)
Where do nociceptive specific cells synapse with?
Only C and Aδ-fibres
What are cells that receive input only from Aβ-fibres?
Proprioceptive
What neurones receive input from all 3 fibre types - Aβ, Aδ and C fibres?
Wide dynamic range neurones
What is the primary transmitter in nociceptors ?
Glutamate
What does glutamate produce in neurotransmission in nociceptors?
A fast epsp and neuronal excitation by activating primarily postsynaptic AMPA receptors with NMDA receptor participation (when afferent input is intense)
What peptides are involved in nociceptive transmission?
Substance P and CGRP causing a slow and prolonged epsp that facilitates activation of NMDA receptors by relieving voltage-dependent block by Mg2+