Pain and Thermosensation Flashcards

1
Q

What is pain?

A

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

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2
Q

What are the 3 forms of pain?

A

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

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3
Q

What are nociceptors?

A

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

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4
Q

Where are nociceptor cell bodies located?

A

In the DRG and trigeminal ganglia (TG)

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5
Q

What order of neurone are nociceptors?

A

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

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6
Q

What makes up nociceptors?

A

Aδ- and C-fibres

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7
Q

Where does nociceptor transduction begin?

A

Free nerve endings- mediated by numerous receptors and channels

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8
Q

What are Aδ fibres?

A

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

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9
Q

What are C-fibres?

A

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

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10
Q

What is frequency coding?

A

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

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11
Q

What are the two types of Aδ- fibres?

A
Type I (HTM: high threshold mechanoreceptors)
Type II
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12
Q

Describe type I Aδ- fibres?

A

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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13
Q

Describe type II Aδ- fibres?

A

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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14
Q

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

A

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

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15
Q

Describe C-MH fibres

A

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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16
Q

Describe C-M fibres

A

Responds to noxious mechanical stimuli

Insensitive to heat and capsaicin

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17
Q

Describe C-H fibres

A

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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18
Q

Describe C-MiHi (silent) fibres

A

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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19
Q

What direction nociceptor signalling?

A

Bidirectional (e.g. peptidergic C-fibres)

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20
Q

Describe the central terminal of the nociceptor

A

Not responsive to environmental stimuli
Site of Ca2+ dependent transmitter release
Targeted by endogenous molecules that regulate activity

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21
Q

Describe the peripheral terminal of nociceptors

A

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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22
Q

Where do nociceptor axons terminate?

A

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

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23
Q

Where do nociceptive C and Aδ-fibres mostly terminate?

A

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

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24
Q

Where do nociceptive specific cells synapse with?

A

Only C and Aδ-fibres

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25
Q

What are cells that receive input only from Aβ-fibres?

A

Proprioceptive

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26
Q

What neurones receive input from all 3 fibre types - Aβ, Aδ and C fibres?

A

Wide dynamic range neurones

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27
Q

What is the primary transmitter in nociceptors ?

A

Glutamate

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28
Q

What does glutamate produce in neurotransmission in nociceptors?

A

A fast epsp and neuronal excitation by activating primarily postsynaptic AMPA receptors with NMDA receptor participation (when afferent input is intense)

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29
Q

What peptides are involved in nociceptive transmission?

A

Substance P and CGRP causing a slow and prolonged epsp that facilitates activation of NMDA receptors by relieving voltage-dependent block by Mg2+

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30
Q

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

A

Peripheral and central sensitisation

31
Q

What is peripheral sensitisation mediated by?

A

Nociceptors at the site of injury/tissue inflammation

32
Q

What does peripheral sensitisation cause?

A

Primary hyperalgesia via:
reduced threshold
amplified response

33
Q

What does peripheral sensitisation require for maintenance?

A

Ongoing peripheral pathology

34
Q

What does peripheral sensitisation play a major role in?

A

Heat, and less so, mechanical sensitivity

35
Q

What does central sensitisation reflect?

A

An increase in CNS neurone activity and properties

36
Q

What does central sensitisation cause?

A

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

37
Q

Central sensitisation underlies pain that persists after what?

A

Tissue healing

38
Q

What does central sensitisation play a major role in?

A

Mechanical sensitivity

39
Q

Where does visceral pain originate from?

A

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

40
Q

How is visceral pain described?

A

Poorly localised and a dull, aching, throbbing character

41
Q

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

A

Sympathetic

42
Q

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

A

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

43
Q

Where do visceral nociceptors terminate?

A

Laminae I and V, but not II

44
Q

What is visceral pain perceived as?

A

At a distance from the affected organ

45
Q

What is visceral pain often associated with?

A

Autonomic features - nausea, vomiting, sweating, pallor

46
Q

What is the area of referral in visceral pain?

A

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

47
Q

How is viscerosomatic pain described?

A

Sharp and well localised

48
Q

When does viscerosomatic pain?

A

When inflammatory exudate from a diseased organ contacts a somatic structure

49
Q

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

A
Spinothalamic tract (STT)
Spinoreticular tract (SRT)
50
Q

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

A

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

51
Q

What does the SRT transmit?

A

Largely slow C-fibre pain

52
Q

What does the SRT connect with?

A

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

53
Q

What is the SRT involved in?

A

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

54
Q

Which is the fast pathway, STT or SRT?

A

STT

55
Q

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

A

The primary sensorimotor cortices by thalamocortical neurones

56
Q

What does the STT act as?

A

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

57
Q

Where does the SRT signal to?

A

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

58
Q

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

A

To limbic areas of the forebrain by thalamocortical neurones

59
Q

What does the SRT do?

A

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

60
Q

Are pain and nociception identical?

A

No

61
Q

When may pain and nociception occur?

A

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

62
Q

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

A

Simultaneous activity in LTMs (Aβ-fibres)

63
Q

What is gate control theory?

A

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

64
Q

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

A

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

65
Q

What can Aβ-fibres be activated by?

A

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

66
Q

Describe the gate status in physiological influences?

A

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

67
Q

Describe the gate status in medical influences?

A

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

68
Q

Describe the gate status in cognitive influences?

A

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

69
Q

Describe the gate status in emotional state influences?

A

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

70
Q

Describe the gate status in behavioural personality influences?

A

Open: Introvert
Closed: Extrovert

71
Q

What are thermoreceptors?

A

Neurones that are specialised to respond to small changes in temperature

72
Q

Is temperature sensitivity uniform across the body surface?

A

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

73
Q

A family of what have been implicated in thermosensation?

A

Transient Receptor Potential (TRP) channels