T2 L7 Physiology of pain

Question 1

What is the definition of pain?

Answer 1

Unpleasant sensory experience accompanied by tissue damage

Accompanied with emotional reaction

Question 2

Why do we feel pain?

Answer 2

Warning sign
Avoid harmful situations
Prevent further injury or death
Tells us to rest following injury

Question 3

What are the different sensations of pain?

Answer 3

Deep ache
Burning
Itchy
Stabbing
Freezing

Question 4

What are the 3 classifications of pain?

Answer 4

Nociceptive
Inflammatory
Neuropathic

Question 5

Describe Aa & Ab fibres

Answer 5

Myelinated
Large diameter
Light touch, proprioception
30-75nm/sec

Question 6

Describe Aδ

Answer 6

Thinly myelinated
Medium diameter
Light touch, temperature, nociception
5-30nm/sec

Question 7

Describe C fibres

Answer 7

Unmyelinated
Small diameter
Temperature, nociception
0.5-2nm/sec

Question 8

What response do Aδ fibres produce?

Answer 8

Sharp pricking pain

Question 9

What response do C fibres produce?

Answer 9

Slow, dull ache or burning pain

Question 10

What can activate nociceptors?

Answer 10

Pressure
Heat
Cold
Chemical
Tissue damage / inflammation

Question 11

What do polymodal nociceptors respond to?

Answer 11

Pressure
Temperature
Chemical

Question 12

Describe the transduction mechanism for pressure

Answer 12

Mechanically sensitive ion channel
Not yet identified in eukaryotic cells
Acid-sensing ion channels (ASIC)
Transient receptor potential (TRP) family of channels

Question 13

Describe the transduction mechanism for temperature?

Answer 13

Transient receptor potential family of channels
6 transmembrane domains
Activated by aromatic agonists

Question 14

What activates TRVP1?

Answer 14

Hot temperatures

Agonist is chilli (capsaicin)

Question 15

Describe the central pain pathway in first order neurons

Answer 15

Enter dorsal horn
Form tract of Lissauer
Synapse in substantia gelatinosa
Glutamate & substance P excite second order neurons

Question 16

Describe the central pain pathway in second order neurons

Answer 16

Cross in dorsal horn at each level

Ascend in anterolateral column to thalamus

Question 17

Describe why referred pain occurs

Answer 17

Convergence of visceral & cutaneous receptors on same second order neurons in spinal cord
Brain perceives pain as cutaneous

Question 18

Describe the central pain pathway in third order neurons

Answer 18

Ascend to primary somatosensory cortex
Encode sensory components e.g. where it hurts & modality
Projections to insula & cingulate cortex to encode emotional components of pain
Pain network

Question 19

What determines pain experience?

Answer 19

Behaviour
Emotions
Past experiences

Question 20

What are 2 important regions in the descending regulation of pain?

Answer 20

Periaqueductal grey matter

Rostral ventromedial medulla

Question 21

Describe the pathway from PAG to dorsal horn

Answer 21

Periaqueductal grey matter projects to rostral ventromedial medulla which projects to dorsal horn
Modulates activity of spinothalamic tract

Question 22

Describe the inhibition of pain

Answer 22

PAG neutrons excite RVM neutrons which inhibit or excite spinothalamic tract
Serotonergic projects act on dorsal horn inhibitory interneurons
Also parallel noradrenalin pathway

Question 23

Where are opioids released from?

Answer 23

Interneurons at multiple sites:

• midbrain (periaqueductal grey matter)
• medulla (rostral ventromedial medulla)
• dorsal horn

Question 24

What do opioids act on?

Answer 24

Inhibitory metabotropic receptors

Question 25

What chemicals are released by tissue damage?

Answer 25

``` ATP H+ Serotonin Histamine Bradykinin Prostaglandins Nerve growth factor ```

Question 26

What does ATP bind to?

Answer 26

Purinergic receptors (P2X)

Question 27

What does H+ bind to?

Answer 27

Acid-sensing ion channels

Question 28

What does serotonin bind to in the activation of nociceptors?

Answer 28

5HT3 receptors

Question 29

What happens when lactic acid builds up?

Answer 29

1) Tissue acidosis 2) Increased H+ 3) Activation of nociceptors 4) Pain

Question 30

What are the causes of neurogenic inflammation?

Answer 30

Vasodilation Increased permeability Activation of mast cells which release histamine causing more inflammation

Question 31

What is allodynia?

Answer 31

Non-noxious stimuli produces a painful response

Question 32

What is hyperalgesia?

Answer 32

Noxious stimuli produce exaggerated pain response

Question 33

What is the benefit of pain hypersensitivity from inflammation?

Answer 33

Pain is more painful | Helps healing by ensuring contact with injured tissue is minimised until repair is complete

Question 34

What are the mechanisms of pain hypersensitivity?

Answer 34

1) Peripheral sensitisation | 2) Central sensitisation

Question 35

Describe peripheral sensitisation

Answer 35

Increase in responsiveness of peripheral ends of nociceptors Driven by tissue injury or inflammation Bradykinin & NGF --> reduce threshold of heat-activated channels.

Question 36

What happens when bradykinin binds to receptor?

Answer 36

Activation of protein kinase --> phosphorylates TRPV1 --> reduces its threshold --> fires more easily

Question 37

What does prostaglandin do?

Answer 37

Reduces threshold of sodium channels