Physiology of pain

Question 1

Nociceptive

Answer 1

Normal functioning of nocioceptors

Question 2

Inflammatory

Answer 2

Pain in response to inflammation

Question 3

Neuropathic

Answer 3

Pain in response to injury in the nervous system

Question 4

Nociceptors

Answer 4

Primary sensory neurones that detect pain

Have free nerve endings in periphery

Question 5

Aδ fibres

Answer 5

Sharp pricking pain

Well localised
Activation of reflex arcs

Question 6

C fibres

Answer 6

Slow dull ache

Burning pain

Poorly localised

Question 7

Activation of nocioceptors

Answer 7

Pressure

Heat

Cold

Chemical

Tissue damage/ inflammation

Question 8

Polymodal nocioceptors

Answer 8

Most C-fibre nocioceptors are polymodal

Respond to pressure, temperature and chemical

Question 9

Transduction mechanisms: pressure

Answer 9

Mechanically sensitive ion channels

Not yet identified in eukaryotic cells

Question 10

Transduction mechanisms: temperature

Answer 10

Transient receptor potential family of channels

Detect different temperatures

Question 11

Spinothalamic tract first order neurones

Answer 11

Enter dorsal horn

Form tract of Lissauer

Synapse in substantia gelatinosa

Question 12

Spintothalamic tract second order neurones

Answer 12

Cross in dorsal horn at each level

Ascend in anterolateral column to thalamus

Question 13

Referred pain

Answer 13

Convergence of visceral and cutaneous nocioceptors on same second order neurones in spinal cord

Brain perceives pain as cutaneous

Question 14

Spinothalamic tract third order neurones

Answer 14

Ascend to primary somatosensory cortex

Projections to insula and cingulate cortex

Question 15

Descending regulation ofpain

Answer 15

Pain experience determined by many factors

Higher cortical regions can activate descending modulatory pathways

Question 16

Important regions in descending regulation of pain

Answer 16

Periaqueductal gray matter

Rostral ventromedial medulla

Question 17

Inhibition of pain

Answer 17

PAG neurones excite RVM neurones which inhibit the spinothalamic tract

Question 18

Endogenous opioid system

Answer 18

Opioids play important role in descending inhibition of pain

Especially stress induced analgesia

Opioids are inhibitors

Question 19

Opioids released from

Answer 19

Midbrain (periaqueductal gray matter)

Medulla (rostral ventromedial medulla)

Dorsal horn

Question 20

Chemicals released as part of tissue damage

Answer 20

ATP

H+

Serotonin/ 5-HT (from platelets)

Histamine (from mast cells)

Bradykinin

Prostaglandin

Nerve growth factor

Question 21

Direct activation of nocioceptors

Answer 21

ATP: binds to purinergic receptors

H+: binds to acid-sensing ion channels

Serotonin: binds to 5-HT3 receptors

Question 22

Neurogenic inflammation

Answer 22

Activation of one branch of nocioceptor axon, triggers release of substance P and CGRP from anther

Causes

• vasodilation
• increased permeability
• activation of mast cells
• release of histamine
• more inflammation

Question 23

Allodynia

Answer 23

Non-noxious stimuli produce a painful response

Question 24

Hyperalgesia

Answer 24

Noxious stimuli produce an exaggerated pain response

Question 25

Peripheral sensitisation

Answer 25

Increase in responsiveness of the peripheral ends of nocioceptors Driven by tissue injury or inflammation Bradykinin and NGF reduce threshold of heat activated channels Prostaglandin reduces threshold of sodium channels

Question 26

Bradykinin

Answer 26

Binds to receptor (metatropic- G protein coupled) Activation of protein kinase phosphorylates TRPV1