Physiology of pain 1

Question 1

Why do we feel pain?

Answer 1

Warning sign - survival
Avoid harmful situations
Prevents further injury or death
Tells us to rest following an injury

Question 2

What are the sensations of pain?

Answer 2

Burning
Stabbing 
Sharp
Radiating
Deep ache
Freezing
Itch

Question 3

What are the 3 classifications of pain?

Answer 3

Nociceptive - normal functioning of nociceptors

Inflammatory - pain in response to inflammation

Neuropathic - Pain in response to injury of nervous system

Question 4

What are nociceptors?

Answer 4

Primary sensory neuron that detects pain
Pseudounipolar - cell body in dorsal root ganglion
From skin, muscle, joints, viscera, meninges to the dorsal horn

Question 5

How are sensory nerve fibres classified?

Answer 5

By diameter and myelin content
Aalpha and Abetea fibres
Adelta fibres
C fibres

Question 6

Describe Aalpha and Abeta nerve fibres

Answer 6

Myelinated
large diameter
light touch and proprioception

Question 7

Describe Adelta fibres

Answer 7

Thinly myelinated
Medium diameter
Light touch, temperature and nociception

Question 8

Describe C fibres

Answer 8

Unmyelinated
Small diameter
Temperature
Nociceptive

Question 9

What do meissner’s detect?

Answer 9

Stroking/fluttering

Question 10

What do pacinicans detect?

Answer 10

Vibration

Question 11

What do merkel’s discs detect?

Answer 11

Pressure

Question 12

What do ruffini detect?

Answer 12

Stretch

Question 13

What does it feel like when Adelta fibre nociceptors respond?

Answer 13

Sharp pricking pain

Question 14

What does it feel like when C fibre nociceptors respond?

Answer 14

Slow dull ache

Burning pain

Question 15

Name the peaks found on an electrophysiology recording of the whole sensory neuron

Answer 15

Aalpha Abeta
Adelta
C fibres

Question 16

Describe the two pain responses

Answer 16

Fast sharp pricking pain - well localised, activation of reflex arcs (Adelta)

Slow dull ache - poorly localised (fibres)

Question 17

What activates nociceptors?

Answer 17

Pressure

Heat

Cold

Chemical

Tissue damage/inflammation

Question 18

Which type of pain has no first response?

Answer 18

Visceral pain

Question 19

What is meant by polymodal nociceptors?

Answer 19

Most C fibres

Respond to pressure, temperature and chemical

Question 20

Describe the transduction mechanism of pressure

Answer 20

• Mechanically sensitive ion channels
• Not yet identified in eukaryotic cells
  Potential channels - acid sensing ion channels, Transient receptor potential family of channels

Question 21

Describe the transduction mechanism of temperature

Answer 21

• Transient receptor potential family of channels

- Detect different temperatures

Question 22

Describe the central pain pathway

Answer 22

Pain information ascends the spinothalamic pathway

Question 23

What is TRPV1?

Answer 23

Vanilloid subtype responds to heat (eg. chilli - capsaicin is and agonist)

Question 24

Describe the spinothalamic tract

Answer 24

First order neuron - Enter dorsal horn, form tract of lissauer, synapse in substantia gelatinosa (lamina 1 and 2)
Glutamate and substance P excites second order neurons

Second order neurons - Cross in the dorsal horn in each level, ascend in anterolateral column to the thalamus

Third order neurons - Ascend to primary somatosensory cortex - encode the sensory components (tells you where it hurts and modality) Lower body to medial cortex and upper body to lateral cortex. Projections to insula and cingulate cortex. Encodes the emotional components of pain (unpleasantness, negative effect)

Question 25

What is referred pain?

Answer 25

Convergence of visceral and cutaneous nociceptors on same second order neurons in spinal cord Brain perceives the pain as cutaneous

Question 26

Describe the descending regulation of pain

Answer 26

Stress induced analgesia - battle victims with no pain | Higher cortical regions can activate descending modulatory pathways

Question 27

Name the two important regions in downregulation of pain

Answer 27

Periaqueductal gray matter (PAG) Rostral ventromedial medulla (RVM) Cortical regions project to PAG PAG projects to RVM RVM projects to dorsal horn Modulates activity of spinothalamic tract

Question 28

How is pain inhibited?

Answer 28

PAG neurons excite RVM neurons which inhibit (or excite) the spinothalamic tract Serotonergic projections act on dorsal horn inhibitory interneurons Also parallel noradrenalin pathway

Question 29

Describe the endogenous opioid system

Answer 29

Opioids play an important role in the descending inhibition of pain (E.g. Endorphins, enkephalins) Especially stressed-induced analgesia Opioids are inhibitory - Act on inhibitory metabotropic receptors Released from interneurons at multiple sites: - Midbrain (Periaqueductal gray matter) - Medulla (Rostral ventromedial medulla) - Dorsal horn

Question 30

Name some chemicals released as part of tissue damage in activating or modulating nociceptors

Answer 30

``` ATP H+ Serotonin/5-HT (from platelets) Histamine (from mast cells) Bradykinin Prostaglandin (conversion of arachidonic acid (lipid) by cyclooxygenase (COX) enzymes) Nerve growth factor ```

Question 31

What is the effect of ATP on nociceptors

Answer 31

Binds to the purinergic receptors P2X Switch on Cause pain

Question 32

What is the effect of H+ on nociceptors

Answer 32

Binds to acid sensing ion channels Switch on Cause pain

Question 33

What is the effect of serotonin on nociceptors

Answer 33

Binds to 5HT3 receptors Switch on Cause pain

Question 34

Describe neurogenic inflammation

Answer 34

Activation of one branch of a nociceptor axon, triggers release of substance P and CGRP from another Causes - Vasodilation, increased permeability, activation of mast cells release of histamine More inflammation

Question 35

What can inflammation do to pain?

Answer 35

Cause pain hypersensitivity - pain is more painful "Pain hypersensitivity after an injury helps healing by ensuring that contact with the injured tissue is minimized until repair is complete”

Question 36

What is Allodynia?

Answer 36

Non-noxious stimuli produce a painful response

Question 37

What is Hyperalgesia

Answer 37

Noxious stimuli produce an exaggerated pain response

Question 38

What are the mechanisms of pain hypersensitivity?

Answer 38

``` Peripheral sensitisation ( hyperalgesia) Central sensitisation (hyperalgesia and allodynia) - mechanism in neuropathic pain ```

Question 39

What is peripheral sensitisation?

Answer 39

Increase in responsiveness of the peripheral ends of nociceptors Driven by tissue injury or inflammation -

Question 40

What chemicals are involved in peripheral sensitisation?

Answer 40

bradykinin and NF reduce the threshold of heat activated channels Prostaglandin reduces threshold of sodium channels

Question 41

Give a common example of peripheral sensitization

Answer 41

Sunburn

Question 42

Describe the action of bradykinin

Answer 42

- Binds to receptor (metabotropic – G protein-coupled) - Activation of protein kinase phosphorylates TRPV1 Phosphorylation of channel reduces its threshold (i.e. it fires more easily)