Pain and Thermosensation

Question 1

what is pain?

Answer 1

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

Question 2

3 forms of pain?

Answer 2

nociceptive (adaptive - immediate protective response, short lived) inflammatory pain (adaptive - assists in healing, lasts days-weeks) pathological (maladaptive - no physiological purpose, lasts months-years-lifetime)

Question 3

pathological pain is defined as what?

Answer 3

pain lasting over 3 months with no physiological cause

Question 4

alternative drug classes used as analgesics (often in neuropathic pain)?

Answer 4

antidepressants (e.g amitriptyline ) anticonvulsants (e.g gabapentin) local anaesthetics

Question 5

what are nociceptive neurones?

Answer 5

primary sensory afferent nerves which can only be activated by intense noxious stimuli (mechanical, chemical or thermal) can also be activated by lesser stimuli in inflammation

Question 6

primary neurotransmitter of nociceptive neurones?

Answer 6

glutamate

Question 7

where are terminals of nociceptive neurones found?

Answer 7

central terminal in CNS

peripheral terminal in peripheral location

Question 8

subtypes of nociceptive neurones?

Answer 8

A delta fibres C fibres

Question 9

describe A delts fibres

Answer 9

mechanical/thermal noceiceptors thinly myelinated respond to noxious thermal and mechanical stimuli mediate first or fast pain - lancinating, stabbing, pricking sensations

Question 10

describe C fibres

Answer 10

unmyelinated collectively respond to all noxious stimuli (polymodal) mediate second or slow pain - burning, throbbing, cramping, aching sensations

Question 11

why is 2nd pain slower to arise?

Answer 11

results from developing inflammatory response so takes time for inflammatory mediators to arise

Question 12

what 3 types of receptor are present at polymodal receptors?

Answer 12

mechanoreceptors (mechanical stimuli) heat/cold sensitive receptors (temperature) ASIC, P2X, P2Y, B2 receptors (chemical stimuli)

Question 13

many types of thermal receptors, what are the main family of thermal receptors?

Answer 13

transient receptor potential (TRP) family

Question 14

nociceptive pathway?

Answer 14

free nerve ending> depolarization > axon > dorsal horn of spinal cord > glutamate released > 2nd order neuron excited > axon crosses over immediately at spinal cord level and ascends spinal cord in spinothalamic and spinoreticulothalamic tracts

Question 15

where is soma of nociceptor neurone found?

Answer 15

dorsal root ganglion

Question 16

peptidergic polymodal nociceptors (subtype of C fibres) hhave afferent and efferent functions, describe the afferent function

Answer 16

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

Question 17

repeated stimulation of the efferent branch of peptidogergic polymodal nociceptors can result in what?

Answer 17

AP is conducted around the terminal branches of the peripheral terminal causing release of peptides - substance P, CGRP

these peptides act as proinflammatory mediators causing inflammation and pain but can also stiulate further APs in the peripheral terminal which travel back to the spinal cord causing perception of pain

= hyperalgesia (slight pain becomes intense pain) and allodynia (pain from non-noxious stimuli)

Question 18

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Answer 18

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Question 19

course of neurogenic inflammation?

Answer 19

peptides released from free nerve ending of peptidergic nociceptor due to tissue damage or inflammatory mediators > SP (peptide) causes - vasodilation and extravasation of plasma proteins promoting formation of bradykinis and prostaglandins - release of histamine from mast cells - sensitises surrounding nociceptors > CGRP induces vasodilation > primary and secondary hyperalgesia and allodynia ensue

Question 20

describe the path of neurotransmission between the primary sensory afferent and 2nd order neurone in the dorsal horn of the spinal cord?

Answer 20

AP > opening go voltage gated calcium channels > calcium influx > glutamate release > activation of glutamate receptors > membrane depolarization > ng of voltage gated sodium channels > AP

Question 21

what are the 2 types of glutamate receptor?

Answer 21

AMPA

NMDA

Question 22

Action of glutamate on each type of glutamate receptor?

Answer 22

AMPA = fast graded e.p.s.p large enough to trigger an AP in the post synaptic cell

NMDA usually blocked by magnesium, when cell is depolarized by AMPA, magneisum moves and opens up NMDA to contribute to synaptic transmission when afferent input is intense (peptides can also remove Mg and cause slight depolarization)

NMDA can allow calcium influx which alters gene transcription in cell causing increased sensitivity to glutamate

Question 23

C fibres path to spinal cord?

Answer 23

synapse on most superior part of dorsal horn (lamina 1) on NS cells and interneurone which has cell body in lamina 2, this interneurone synpases on WDR neurone

Question 24

path of A delta fibres?

Answer 24

synapse on lamina 1, 2 and directly on WDR neurones

Question 25

path of A beta fibres?

Answer 25

loop round and synapse on medial side of laminas 3, 4, and 5

Question 26

paradox of A beta fibres synapse?

Answer 26

A beta fibres are non noxious but synapse on same cells (WDR) as fibres carryinf noxious stimuli (A delta and C) brain could get confused

Question 27

what are WDR neurones?

what are A beta fibres?

Answer 27

wide dynamic range neurones

recieve input from all 3 types of fibre so respond to wide range of stimuli

A beta fibres carry information about touch

Question 28

visceral pain comes from what actions of the viscera?

Answer 28

stretching, twisting, inflammation and ischaemia (not cutting or burning) originates from nociceptors covering tissues (peritoneum, pleura etc)

Question 29

path of visceral pain?

Answer 29

visceral afferents follow sympathetic pathways before entering the dorsal horn

Question 30

how can visceral pain be felt as cutaneous?

Answer 30

some visceral and cutaneous affernts converge upon the sam spinothalamic neurones in the spinal cord (all cells with a visceral RF also have a separate cutaneous RF)

Question 31

visceral vs viscerosomatic pain?

Answer 31

visceral = poorly localised, often associated autonomic features, often referred, consistent viscerosomatic = sharp and well localised, occurs when inflammatory exudate from diseased organ contacts somatic (body wall) structures, pathology may be present with diffuse visceral pain that progresses to sharp viscerosomatic pain

Question 32

pain vs nociception?

Answer 32

pain = awareness of suffering, can occur in the absence of nociception or can have nociception with no pain nociception = may occur in the absence of pain, just the conduction of a noxious (or even non-noxious) stimulus

Question 33

describe the gate control theory?

Answer 33

physiological gate in spinal cord when open, nociceptive signals can enter dorsal horn and ascend spinal cord if closed, even the most intense stimuli cant enter (no pain felt) whether open/closed depends on the activity of A beta fibres compared to A delta and c fibres - high A beta activity by comparison = closed (explains phenomenon why pain isn’t felt if heavily distracted)

Question 34

where is the “gate” located?

Answer 34

substantia gelatinosa

Question 35

how does the gate work?

Answer 35

AB synapse on projection neurone which could cause pain, however an earlier branch of AB excites inhibitory interneurone which inhibits action of projection neurone

AD and C fibres also synapse on projection neurone and can cause pain. The earlier branch of these fibres however is inhibitory in nature so inhibits the inhibitory interneurone, so the projection neurone is not inhibited so is therefore excited and pain can be percieved