Physiology and Pharmacology 5 - Pain

Question 1

What is pain?

Answer 1

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

Question 2

What are the 3 forms of pain?

Answer 2

Nociceptive pain
Inflammatory pain
Pathological pain

Question 3

What of the 3 forms of pain are adaptive?

Answer 3

Nociceptive and inflammatory pain = adaptive

Pathological pain = maladaptive

Question 4

What are nociceptors?

Answer 4

Specific peripheral primary sensory afferent enrolees normally activated preferentially by intense stimuli e.g. thermal, mechanical, chemical, that are noxious

Question 5

Are nociceptors first or second order neurones?

Answer 5

First order neurones (they relay information to second order neurones in the CNS by chemical synaptic transmission)

Question 6

What are first order neurones?

Answer 6

Neurones that conduct impulses from receptors of the skin and from proprioceptors, to the spinal cord or brain stem, where they synapse with second order neurones

Question 7

What is adaptive pain?

Answer 7

Helpful pain that produces behaviour that promotes healing and recovery (compared with maladaptive pain)

Question 8

Why can nociceptive pain be described as adaptive?

Answer 8

It serves as an early warning system to detect and minimise contact with damaging stimuli (noxious events)

Question 9

Threshold of nociceptive pain?

Answer 9

High threshold - provoked only by intense stimuli that activate nociceptors

Question 10

Features of nociceptive pain? (5)

Answer 10

Overrides most other ongoing activities of the nervous system
Initiates a withdrawal reflex
Extremely unpleasant
Engages adverse emotional components
Serves to inscribe memories that allow avoidance of harm in the future

Question 11

What causes inflammatory pain?

Answer 11

Activation of the immune system in injury, or infection

Question 12

what does activation of the immune system in injury, or infection, cause in terms of inflammatory pain? (2)

Answer 12

Pain hypersensitivity (heightened sensitivity to noxious stimuli)
Allodynia (innocuous stimuli now elicit pain)

Question 13

How is inflammatory pain protective and adaptive?

Answer 13

Assists in the healing of a damaged body part by:
Discouraging physical contact e.g. a wound
Discouraging movement e.g. an inflamed joint

Question 14

What causes pathological pain?

Answer 14

Abnormal nervous system function

Question 15

2 types of pathological pain?

Answer 15

Neuropathic

Dysfunctional

Question 16

What causes neuropathic pain?

Answer 16

peripheral nerve damage

Question 17

What causes dysfunctional pain?

Answer 17

No identified cause

Question 18

What type of fibres are nociceptors either?

Answer 18

Aδ- and C-fibres (not all Aδ- and C-fibres are nociceptors)

Question 19

What type of nociceptors are Aδ- fibres?

Answer 19

Mechanical/ thermal nociceptors

Question 20

Myelination of Aδ- fibres?

Answer 20

Thinly myelinated

Question 21

What type of stimuli do Aδ- fibres respond to?

Answer 21

Noxious mechanical and thermal stimuli

Question 22

What type of pain do Aδ-fibres mediate?

Answer 22

First/ fast pain

Question 23

Myelination of C-fibres?

Answer 23

Unmyelinated

Question 24

What type of stimuli do C-fibres respond to?

Answer 24

All noxious stimuli

Question 25

What type of pain do C-fibres cause?

Answer 25

Second/ slow pain

Question 26

4 examples of receptors that pick up chemical stimuli on polymodal nociceptors?

Answer 26

ASIC P2X P2 B2 receptors

Question 27

Example of a thermal receptor that is activated by noxious heat? What happens to this in inflammation?

Answer 27

Members of the transit receptor potential (TRP) family - particularly TRPV1 Greatly sensitised in inflammation to become active at body temperature

Question 28

What ion channel (chemical receptor) does H+ activate?

Answer 28

Acid sensing ion channel (ASICs)

Question 29

What ion channel (chemical receptor) does ATP activate?

Answer 29

P2X and P2Y receptors

Question 30

What ion channel (chemical receptors) does bradykinin activate?

Answer 30

B2 receptors

Question 31

What happens when a stimulus (mechanical, thermal or chemical) activates a receptor?

Answer 31

It open ion channels (cation selective) in nerve terminal to elicit a depolarisaiton receptor (or generatory) potnetial

Question 32

What is amplitude of generator potential proportional to?

Answer 32

Stimulus intensity (it is graded)

Question 33

What does local current flow (hermann currents) in a sensory neurone terminal trigger?

Answer 33

all or none action potentials at a frequency proportion to the amplitude of the receptor potential

Question 34

What type of signals do c-polymodal nociceptors pick up?

Answer 34

Thermal, chemical and mechanical stimuli

Question 35

What temperature stimulates c-polymodal fibres?

Answer 35

43 degrees C

Question 36

What temperature stimulates type I Aδ-fibres?

Answer 36

53 degrees C

Question 37

What temperature stimulates type II Aδ-fibres?

Answer 37

43 degrees C

Question 38

Where does the first order and second order neurone synapse in the nociceptive pathway?

Answer 38

in the dorsal (posterior) horn of the spinal cord

Question 39

What is the name of the subset of C-fibres that have both afferent and efferent functions?

Answer 39

Peptidergic polymodal nociceptors

Question 40

How do afferent peptidergic polymodal nociceptors transmit nociceptive information to the CNS?

Answer 40

Via release of glutamate and peptides (substance p, Neurokinin A) within the dorsal horn

Question 41

What do efferent peptidergic polymodal nociceptors do?

Answer 41

Release pro-inflammatory mediators e.g. substance P, calcitonin gene-related peptide (CGRP) from peripheral terminals - contributes to neurogenic inflammation

Question 42

What does noxious stimulation of peptidergic polymodal nociceptors do in the long term?

Answer 42

Increases spinal excitability contributing to hyperalgesia and allodynia

Question 43

What are released from free nerve endings of peptidergic nociceptor due to tissue damage?

Answer 43

Peptides (SP and CGRP) or inflammatory mediators

Question 44

What does substance P (released from peptidergic nociceptors due to tissue damage) cause?

Answer 44

Vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins) Release of histamine from mast cells Sensitised surrounding nociceptors

Question 45

What does CGRP released from free nerve endings of peptidergic nociceptors cause?

Answer 45

Vasodilation

Question 46

What does the release of SP and CGRP, or inflammatory mediators, from peptidergic nociceptors due to tissue damage cause? (neurogenic inflammation)

Answer 46

primary and secondary hyperalgesia and allodynia

Question 47

What happens when the action potential arrives at the terminal of the primary afferent neurone?

Answer 47

Opening of voltage-gated Ca2+ channels occurs Ca2+ influx glutamate release

Question 48

What happens to glutamate released by the primary afferent neurone in the dorsal horn?

Answer 48

It activates glutamate receptors on the projection neurone in the distal horn causing membrane depolarisation This leads to the opening of voltage-gated Na+ channels and the production of the action potential

Question 49

Aside from glutamate, what else is involved in neurotransmission between the primary afferent and second order neurone in the dorsal horn?

Answer 49

petides - substance P and CGRP (cause a slow prolonged e.p.s.p. that facilitates activation of NMDA receptors by relieving voltage-dependent block by Mg2+

Question 50

Where are primary afferent cell bodies located? | What is the exception to this?

Answer 50

Dorsal root ganglia | Apart from the trigeminal syste

Question 51

Where do primary afferent axons terminate?

Answer 51

Centrally in the dorsal horn of the spinal cord in various laminae of Rexed

Question 52

What laminae in the spinal cord do nociceptive C and Aδ fibres terminate?

Answer 52

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

Question 53

What do nociceptive specific cells only synapse with?

Answer 53

C and Aδ fibres

Question 54

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

Answer 54

Proprioceptive

Question 55

What do wide dynamic range neurones receive input from?

Answer 55

All 3 types of fibre - therefore respond to a wide range of stimuli

Question 56

Second order nociceptive neurones ascend the spinal cord in the anterolateral system comprising mainly of?

Answer 56

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

Question 57

Where do projection neurones originating from lamina I (fast fibre Aδ pain) terminate?

Answer 57

Posterior nucleus of the thalamus

Question 58

Where do projection neurones originating from lamina V (WDR neurones) terminate?

Answer 58

Posterior and ventroposterior nucleus of the thalamus

Question 59

What type of pain does the spinoreticular tract largely transmit?

Answer 59

Slow C-fibre pain