Pain and Thermosensation Flashcards by Aaron Duff

What is pain?

An unpleasant sensory and emotional experience, associated with actual tissue damage or described in terms of such damage

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What are the 3 forms of pain?

Nociceptive (acute) pain
Inflammatory (prolonged) pain
Pathological (neurogenic) pain

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What are nociceptors?

Specific peripheral primary sensory afferent neurones normally activated preferentially by intense stimuli that are noxious or damaging

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Where are nociceptor cell bodies located?

In the DRG and trigeminal ganglia (TG)

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What order of neurone are nociceptors?

First order that relay information to second order neurones in the CNS by chemical synaptic transmission

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What makes up nociceptors?

Aδ- and C-fibres

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Where does nociceptor transduction begin?

Free nerve endings- mediated by numerous receptors and channels

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What are Aδ fibres?

Mechanical/thermal nociceptors that are thinly myelinated-respond to noxious mechanical and thermal stimuli. Mediate first/fast pain

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What are C-fibres?

Nociceptors that are unmyelinated- collectively they respond to all noxious stimuli (polymodal). Mediate second/slow pain

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What is frequency coding?

The rate of AP discharge correlates with the intensity of the applied stimulus

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What are the two types of Aδ- fibres?

Type I (HTM: high threshold mechanoreceptors)
Type II

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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

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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

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What are the sub-types of C-fibres (H=heat, M=mechano)?

C-MH
C-M
C-H
C-MiHi (silent)

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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

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Describe C-M fibres

Responds to noxious mechanical stimuli

Insensitive to heat and capsaicin

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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

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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

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What direction nociceptor signalling?

Bidirectional (e.g. peptidergic C-fibres)

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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

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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

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Where do nociceptor axons terminate?

Centrally in the orsal horn of the spinal cord in various laminae of Rexed (I-V)

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Where do nociceptive C and Aδ-fibres mostly terminate?

Superficially in laminae I and II (also V for Aδ-fibres)

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Where do nociceptive specific cells synapse with?

Only C and Aδ-fibres

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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+

What are the two processes which cause sensitisation of the nociceptive pathway following tissue damage?

Peripheral and central sensitisation

What is peripheral sensitisation mediated by?

Nociceptors at the site of injury/tissue inflammation

What does peripheral sensitisation cause?

Primary hyperalgesia via: reduced threshold amplified response

What does peripheral sensitisation require for maintenance?

Ongoing peripheral pathology

What does peripheral sensitisation play a major role in?

Heat, and less so, mechanical sensitivity

What does central sensitisation reflect?

An increase in CNS neurone activity and properties

What does central sensitisation cause?

Secondary hyperalgesia and allodynia via: recruitment of novel inputs to nociceptive pathways (e.g. LTMS (Aβ-fibres) abnormal processing of sensory input

Central sensitisation underlies pain that persists after what?

Tissue healing

What does central sensitisation play a major role in?

Mechanical sensitivity

Where does visceral pain originate from?

Nociceptors covering tissues (e.g. peritoneum, pleura) or walls of hollow organs. Due to stretching, twisting, inflammation and ischaemia, but not cutting or burning.

How is visceral pain described?

Poorly localised and a dull, aching, throbbing character

What pathways do visceral afferents from nociceptors follow before entering dorsal horn?

Sympathetic

What do some visceral and skin afferents converge on as all cells with a visceral receptive field also have a separate cutaneous RF?

The same spinothalamic neurones (causes referred pain as brain interprets visceral pain as arising from area of skin)

Where do visceral nociceptors terminate?

Laminae I and V, but not II

What is visceral pain perceived as?

At a distance from the affected organ

What is visceral pain often associated with?

Autonomic features - nausea, vomiting, sweating, pallor

What is the area of referral in visceral pain?

Segmental dermatome (e.g. heart T1-5, gallbladder C4)

How is viscerosomatic pain described?

Sharp and well localised

When does viscerosomatic pain?

When inflammatory exudate from a diseased organ contacts a somatic structure

What are the two nociceptive tracts which make up the anterolateral system?

``` Spinothalamic tract (STT) Spinoreticular tract (SRT) ```

Where do projection neurones in the STT originating from Lamina I (fast fibre Aδ pain) and V (WDR neurones) terminate?

I: Posterior nucleus of the thalamus V: Posterior and ventroposterior nucleus of the thalamus Pain perception in both pathways

What does the SRT transmit?

Largely slow C-fibre pain

What does the SRT connect with?

Reticular nuclei in the brainstem (e.g. periaqueductal grey (PAG) and parabrachial nucleus (PB)

What is the SRT involved in?

Autonomic responses to pain, arousal, emotional responses, fear of pain

Which is the fast pathway, STT or SRT?

STT

In the STT where are signals from the thalamus relayed to?

The primary sensorimotor cortices by thalamocortical neurones

What does the STT act as?

A warning system by signalling the exact location and severity of injury and the duration of pain- also analyses features of the pain

Where does the SRT signal to?

The intralaminar nuclei of the thalamus indirectly through brainstem reticular formation via reticulothalamic tracts

In the SRT where are signals from the thalamus relayed to?

To limbic areas of the forebrain by thalamocortical neurones

What does the SRT do?

Registers the emotional/motivational component of pain, its inherent unpleasantness, anguish and suffering

Are pain and nociception identical?

When may pain and nociception occur?

Pain is awareness of suffering, nociception may occur in the absence of pain and vice versa

What can pain evoked by activity in nociceptors be reduced by?

Simultaneous activity in LTMs (Aβ-fibres)

What is gate control theory?

Certain neurones within substantial gelatinosa project to STT and are excited by both large diameter (Aβ) sensory axons and unmyelinated (C/Aδ) nociceptive axons. These neurone inputs are inhibition by an interneurone and this is excited by the large sensory axon and inhibited by the nociceptive axon. Activity in the nociceptive axon alone maximally excites the projection neurone, allowing nociceptive signals to arise to the brain

What does stimulation of non-nociceptive afferents (e.g. Aβ-fibres) activate?

Directly/indirectly lamina II inhibitory interneurons that suppress firing of the projection neurone

What can Aβ-fibres be activated by?

High frequency, low intensity electrical stimulation through the skin using battery devices (Transcutaneous Electrical Nerve Stimulation)

Describe the gate status in physiological influences?

Open: C/Aδ fibres active Closed: Aβ fibres active

Describe the gate status in medical influences?

Open: Extent of injury, insufficient medication Closed: Sufficient medication

Describe the gate status in cognitive influences?

Open: Focus on pain Closed: Distraction, reinterpretation of pain

Describe the gate status in emotional state influences?

Open: Anxiety, fear, stress, depression Closed: Happy, optimistic, relaxed, rested, prior experience of pain

Describe the gate status in behavioural personality influences?

Open: Introvert Closed: Extrovert

What are thermoreceptors?

Neurones that are specialised to respond to small changes in temperature

Is temperature sensitivity uniform across the body surface?

No- thusly meaning separate warm/cod neurones and associated receptors/channels exist

A family of what have been implicated in thermosensation?

Transient Receptor Potential (TRP) channels