An introduction to pain and thermosensation

Question 1

What are the three forms of pain?

Answer 1

Nociceptive
Inflammatory
Pathological

Question 2

What activates nociceptors?

Answer 2

Intense stimuli (thermal, mechanical, chemical)

Question 3

Nociceptors are _____ ____ ______ that relay information to _____ ____ ______ in the CNS by ________ synaptic transmission

Answer 3

Nociceptors are first order neurones that relay information to second order neurones in the CNS by chemical synaptic transmission

Question 4

What fibres are found within nociceptors?

Answer 4

Aδ- and C-fibres

Question 5

What kind of fibres are Aδ?

Answer 5

Mechanical/thermal nociceptors

Question 6

Describe the structure and speed of conduction of Aδ fibres?

Answer 6

Thinly myelinated, conduction velocity of 6-30ms-1

Question 7

What kind of fibres are C?

Answer 7

Respond to all noxious stimuli

Question 8

Describe the structure and speed of conduction of C fibres?

Answer 8

0.5-2ms-1

unmyelinated

Question 9

C fibres mediate ____ or ____ pain and Aδ fibres mediate _____ or ____ pain

Answer 9

C fibres mediate second or slow pain and Aδ fibres mediate first or fast pain

Question 10

Give examples of first pain stimuli?

Answer 10

Lancinating, stabbing, pricking

Question 11

Give examples of second pain stimuli?

Answer 11

Burning, throbbing, cramping, aching

Question 12

Thermal stimuli activates which nociceptors?

Answer 12

Transient Receptor potential family, particularly TRPA1, TRPC3, TRPV1

Question 13

Chemical stimuli activates which nociceptors

Answer 13

H+ activates acid sensing ion channels (ASICs)

Question 14

What nociceptors does ATP activate

Answer 14

P2X and P2Y

Question 15

What nociceptors does bradykinin activate?

Answer 15

bradykinin activates B2 receptors

Question 16

Describe the nociceptive pathway

Answer 16

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

Question 17

What are the subsets of peptidergic polymodal nociceptors (subset of C fibres)

Answer 17

Afferent and efferent

Question 18

Describe the function of afferent nociceptors

Answer 18

Transmit nociceptive info to the CNS via release of glutamate and peptides (substance P, neurokinin A) within the dorsal horn

Question 19

Describe the function of efferent nociceptors

Answer 19

Release pro-inflammatory mediators e.g. calcitonin gene-related peptide or substance p, from peripheral terminals contributing to neurogenic inflammation

Question 20

Noxious stimulation in the long term causes what?

Answer 20

Increased spinal excitability contributing to hyperalgesia and allodynia

Question 21

What does substance P cause in neurogenic inflammation?

Answer 21

Vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins)

Question 22

What is the role of histamine in neurogenic inflammation?

Answer 22

Sensitises surrounding nociceptors

Question 23

What does CGRP cause in neurogenic inflammation?

Answer 23

Vasodilation

Question 24

What facilitates neurotransmission between the primary afferent and second order neurone in the dorsal horn

Answer 24

• 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

Question 25

How does a slow and prolonged e.p.s.p by peptide facilitate activation of NMDA receptors?

Answer 25

By relieving voltage-dependent block by Mg2+

Question 26

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 _____

Answer 26

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

Question 27

Nociceptive C- and Aδ-fibres mostly terminate superficially in laminae _ and __ (and also V for __-fibres)

Answer 27

Nociceptive C- and Aδ-fibres mostly terminate superficially in laminae I and II (and also V for Aδ-fibres)

Question 28

Nociceptive specific (NS) cells synapse only with _- and __-fibres

Answer 28

Nociceptive specific (NS) cells synapse only with C- and Aδ-fibres

Question 29

Cells that receive input from only Aβ-fibres are ___________?

Answer 29

Cells that receive input from only Aβ-fibres are proprioceptive

Question 30

Wide dynamic range (WDR) neurones receive input from all _____ types of fibre and thus respond to a wide range of stimuli

Answer 30

Wide dynamic range (WDR) neurones receive input from all three types of fibre and thus respond to a wide range of stimuli

Question 31

What structures does visceral pain originate from?

Answer 31

Nociceptors covering tissues (peritoneum or pleura), or walls of hollow organs.

Question 32

What events does visceral pain originate from?

Answer 32

Stretching, twisting, inflammation and ischaemia- not cutting or burning

Question 33

What does visceral pain tend to present as?

Answer 33

Poorly localised, dull, aching, throbbing

Question 34

Visceral afferents from nociceptors follow __________ pathways before entering the ______ horn

Answer 34

Visceral afferents from nociceptors follow sympathetic pathways before entering the dorsal horn

Question 35

Terminals of visceral nociceptors terminate in laminae _ and _, but not _

Answer 35

Terminals of visceral nociceptors terminate in laminae I and V, but not II

Question 36

What is referred pain?

Answer 36

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

Question 37

Where is visceral pain perceived?

Answer 37

At a distance from the affected organ

Question 38

What is visceral pain associated with?

Answer 38

Autonomic features | -nausea, vomiting, sweating, pallor

Question 39

The area of pain referral is to where?

Answer 39

The segmental dermatome e.g. heart T1-5, Gallbladder C4

Question 40

What may be seen in the segmental dermatome of pain referral?

Answer 40

Hyperalgesia

Question 41

When does viscerosomatic pain occur?

Answer 41

occurs when inflammatory exudate from a diseased organ contacts a somatic (body wall) structure (e.g. parietal peritoneum)

Question 42

Pain evoked by activity in nociceptors (C and Aδ fibres) can be reduced by what?

Answer 42

Simultaneous activity in low threshold mechanoreceptors Aβ-fibres

Question 43

Signals from Aβ-fibres, and C/Aδ fibres are processed by neuronal circuits of the?

Answer 43

Substantia gelatinosa

Question 44

When Aβ-fibre activity is greater than that of C/Aδ fibres what happens?

Answer 44

The spinal gate is closed and synaptic transmission of nociceptive signals to the ascending tracts is suppressed and pain is not perceived

Question 45

When C/Aδ-fibre activity is greater than that of Aβ fibres what happens?

Answer 45

The spinal gate is open and synaptic transmission of nociceptive signals to the ascending traces is facilitated and pain is perceived

Question 46

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

Answer 46

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

Question 47

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

Answer 47

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

Question 48

In gate control theory; activity in the _______ axon alone maximally excites the projection neurone, allowing nociceptive signals to arise to the _____

Answer 48

activity in the nociceptive axon alone maximally excites the projection neurone, allowing nociceptive signals to arise to the brain

Question 49

Second order neurones ascend the spinal cord in the anterolateral system comprising mainly; The ________ tract (S__) The ________ tract (S__)

Answer 49

Second order neurones ascend the spinal cord in the anterolateral system comprising mainly; The spinothalamic tract (STT) The spinoreticular tract (SRT)

Question 50

In the spinothalamic tract projection neurones originating from lamina _ (fast fibre __ pain) terminate in the ______ _______ of the _______

Answer 50

In the spinothalamic tract projection neurones originating from lamina I (fast fibre Aδ pain) terminate in the posterior nucleus of the thalamus

Question 51

In the spinothalamic tract projection neurones originating from lamina _ (WDR neurones) terminate in _______ and __________ ______ of the ______

Answer 51

In the spinothalamic tract projection neurones originating from lamina V (WDR neurones) terminate in posterior and ventroposterior nucleus of the thalamus

Question 52

In the spinothalamic tract what is required for pain perception to occur?

Answer 52

Stimulus firing in both pathways (Fast fibre Aδ and WDR)

Question 53

The spinoreticular tract largely transmits ____ _ fibre pain

Answer 53

The spinoreticular tract largely transmits slow C fibre pain

Question 54

What does the spinoreticular tract make extensive connections with?

Answer 54

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

Question 55

The spinoreticular tract is involved in ______ responses to pain, _____, _______ responses, ____ of pain

Answer 55

The spinoreticular tract is involved in autonomic responses to pain, arousal, emotional responses, fear of pain