An introduction to pain and thermosensation Flashcards
What are the three forms of pain?
Nociceptive
Inflammatory
Pathological
What activates nociceptors?
Intense stimuli (thermal, mechanical, chemical)
Nociceptors are _____ ____ ______ that relay information to _____ ____ ______ in the CNS by ________ synaptic transmission
Nociceptors are first order neurones that relay information to second order neurones in the CNS by chemical synaptic transmission
What fibres are found within nociceptors?
Aδ- and C-fibres
What kind of fibres are Aδ?
Mechanical/thermal nociceptors
Describe the structure and speed of conduction of Aδ fibres?
Thinly myelinated, conduction velocity of 6-30ms-1
What kind of fibres are C?
Respond to all noxious stimuli
Describe the structure and speed of conduction of C fibres?
0.5-2ms-1
unmyelinated
C fibres mediate ____ or ____ pain and Aδ fibres mediate _____ or ____ pain
C fibres mediate second or slow pain and Aδ fibres mediate first or fast pain
Give examples of first pain stimuli?
Lancinating, stabbing, pricking
Give examples of second pain stimuli?
Burning, throbbing, cramping, aching
Thermal stimuli activates which nociceptors?
Transient Receptor potential family, particularly TRPA1, TRPC3, TRPV1
Chemical stimuli activates which nociceptors
H+ activates acid sensing ion channels (ASICs)
What nociceptors does ATP activate
P2X and P2Y
What nociceptors does bradykinin activate?
bradykinin activates B2 receptors
Describe the nociceptive pathway
Noxious stimulation of free nerve ending —> action potential in axon of nociceptor –> enters dorsal horn of spinal cord —> projects to second order neurone —> spinothalamic and spinoreticulothalamic tracts
What are the subsets of peptidergic polymodal nociceptors (subset of C fibres)
Afferent and efferent
Describe the function of afferent nociceptors
Transmit nociceptive info to the CNS via release of glutamate and peptides (substance P, neurokinin A) within the dorsal horn
Describe the function of efferent nociceptors
Release pro-inflammatory mediators e.g. calcitonin gene-related peptide or substance p, from peripheral terminals contributing to neurogenic inflammation
Noxious stimulation in the long term causes what?
Increased spinal excitability contributing to hyperalgesia and allodynia
What does substance P cause in neurogenic inflammation?
Vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins)
What is the role of histamine in neurogenic inflammation?
Sensitises surrounding nociceptors
What does CGRP cause in neurogenic inflammation?
Vasodilation
What facilitates neurotransmission between the primary afferent and second order neurone in the dorsal horn
- glutamate : fast e.p.s.p and neuronal excitation by activating postsynaptic AMPA receptors with NMDA receptor participation
- peptides (substance P and GCRP): slow e.p.s.p that facilitates activation of NMDA receptors
How does a slow and prolonged e.p.s.p by peptide facilitate activation of NMDA receptors?
By relieving voltage-dependent block by Mg2+
Primary afferent cell bodies (apart from the trigeminal system) are located in the ______ ____ ______ (___). Axon terminates centrally in the dorsal horn of the spinal cord in various ______ of _____
Primary afferent cell bodies (apart from the trigeminal system) are located in the dorsal root ganglia (DRG). Axon terminates centrally in the dorsal horn of the spinal cord in various laminae of Rexed
Nociceptive C- and Aδ-fibres mostly terminate superficially in laminae _ and __ (and also V for __-fibres)
Nociceptive C- and Aδ-fibres mostly terminate superficially in laminae I and II (and also V for Aδ-fibres)
Nociceptive specific (NS) cells synapse only with _- and __-fibres
Nociceptive specific (NS) cells synapse only with C- and Aδ-fibres
Cells that receive input from only Aβ-fibres are ___________?
Cells that receive input from only Aβ-fibres are proprioceptive
Wide dynamic range (WDR) neurones receive input from all _____ types of fibre and thus respond to a wide range of stimuli
Wide dynamic range (WDR) neurones receive input from all three types of fibre and thus respond to a wide range of stimuli
What structures does visceral pain originate from?
Nociceptors covering tissues (peritoneum or pleura), or walls of hollow organs.
What events does visceral pain originate from?
Stretching, twisting, inflammation and ischaemia- not cutting or burning
What does visceral pain tend to present as?
Poorly localised, dull, aching, throbbing
Visceral afferents from nociceptors follow __________ pathways before entering the ______ horn
Visceral afferents from nociceptors follow sympathetic pathways before entering the dorsal horn
Terminals of visceral nociceptors terminate in laminae _ and _, but not _
Terminals of visceral nociceptors terminate in laminae I and V, but not II
What is referred pain?
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 – the phenomenon of referred pain
Where is visceral pain perceived?
At a distance from the affected organ
What is visceral pain associated with?
Autonomic features
-nausea, vomiting, sweating, pallor
The area of pain referral is to where?
The segmental dermatome e.g. heart T1-5, Gallbladder C4
What may be seen in the segmental dermatome of pain referral?
Hyperalgesia
When does viscerosomatic pain occur?
occurs when inflammatory exudate from a diseased organ contacts a somatic (body wall) structure (e.g. parietal peritoneum)
Pain evoked by activity in nociceptors (C and Aδ fibres) can be reduced by what?
Simultaneous activity in low threshold mechanoreceptors Aβ-fibres
Signals from Aβ-fibres, and C/Aδ fibres are processed by neuronal circuits of the?
Substantia gelatinosa
When Aβ-fibre activity is greater than that of C/Aδ fibres what happens?
The spinal gate is closed and synaptic transmission of nociceptive signals to the ascending tracts is suppressed and pain is not perceived
When C/Aδ-fibre activity is greater than that of Aβ fibres what happens?
The spinal gate is open and synaptic transmission of nociceptive signals to the ascending traces is facilitated and pain is perceived
In gate control theory; Certain neurones (_) within the _______ ________ project to the _________ tract and are postulated to be excited by both large diameter (__) sensory axons and unmyelinated (___) nociceptive axons
Certain 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
In gate control theory;
The projection neurone (P) inputs are inhibited by an _________ (_) and the ________ is excited by the large sensory axon and inhibited by the _______ axon
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
In gate control theory;
activity in the _______ axon alone maximally excites the projection neurone, allowing nociceptive signals to arise to the _____
activity in the nociceptive axon alone maximally excites the projection neurone, allowing nociceptive signals to arise to the brain
Second order neurones ascend the spinal cord in the anterolateral system comprising mainly;
The ________ tract (S__)
The ________ tract (S__)
Second order neurones ascend the spinal cord in the anterolateral system comprising mainly;
The spinothalamic tract (STT)
The spinoreticular tract (SRT)
In the spinothalamic tract projection neurones originating from lamina _ (fast fibre __ pain) terminate in the ______ _______ of the _______
In the spinothalamic tract projection neurones originating from lamina I (fast fibre Aδ pain) terminate in the posterior nucleus of the thalamus
In the spinothalamic tract projection neurones originating from lamina _ (WDR neurones) terminate in _______ and __________ ______ of the ______
In the spinothalamic tract projection neurones originating from lamina V (WDR neurones) terminate in posterior and ventroposterior nucleus of the thalamus
In the spinothalamic tract what is required for pain perception to occur?
Stimulus firing in both pathways (Fast fibre Aδ and WDR)
The spinoreticular tract largely transmits ____ _ fibre pain
The spinoreticular tract largely transmits slow C fibre pain
What does the spinoreticular tract make extensive connections with?
Reticular nuclei in the brainstem (e.g. periaqueductal grey (PAG) and parabrachial nucleus (PBN))
The spinoreticular tract is involved in ______ responses to pain, _____, _______ responses, ____ of pain
The spinoreticular tract is involved in autonomic responses to pain, arousal, emotional responses, fear of pain
