Pain Physiology

Question 1

What receptors are responsible for pain and itch transmission?

Answer 1

Nociceptors

Question 2

What are two examples of nociceptors?

Answer 2

1. Vanilloid receptors, which respond to damaging heat / capsaicin
2. TRPM8 receptors, which respond to damaging cold / menthol

Question 3

How are nociceptors sensitised?

Answer 3

1. Noxious stimuli cause free nerve endings to release substance P and CRGP
2. These neuropeptides stimulate mast cells to release histamine + bradykinin
3. These neuropeptides also stimulate vasodilation, resulting in more inflammatory molecules being released
4. Noxious stimuli itself also causes prostaglandin and serotonin release
5. All these inflammatory mediators lower nociceptors’ activation threshold, thus sensitising them

Question 4

What two pathways do nociceptors activate?

Answer 4

1. Reflexive protective responses, which are integrated at SC
2. Ascending pathways to cerebral cortex, for conscious pain / itch sensation

Question 5

Describe the general stages of ascending pain transmission.

Answer 5

1. Dorsal horn synapse
2. Central sensitisation
3. Gate control modulation
4. Spinothalamic pathway
5. Descending modulation

Question 6

Describe the dorsal horn synapse stage of pain transmission.

Answer 6

1. Afferent nociceptive fibers synapse onto neurons in the spinal cord
2. They release glutamate, substance P, and GRP to act on the AMPA / NMDA, NK1, and CGRP receptors respectively
3. Receptor activation leads to Na+ influx, thus generating an action potential

Question 7

Describe the central sensitisation stage of pain transmission. (ENHANCES pain)

Answer 7

1. Repeat nociceptive stimulation leads to repeat AMPA receptor activation
2. Normally, the NMDA receptor is inactivate due to blockade of channels by Mg2+
3. Sustained depolarisation releases Mg2+ block, thus allowing NMDA receptor to be activated
4. This allows Ca2+ to enter the cell, thus enhancing pain sensation

Question 8

Describe the gate control modulation stage in pain transmission. (SUPPRESSES pain)

Answer 8

1. normally, tonically-active inhibitory interneurons in the spinal cord inhibit ascending pathways
2. C-fibers synapse onto inhibitory interneurons, allowing them to excite the ascending tract + block tonic inhibition
3. However, A-beta fibers (stimulated by rubbing) synapse onto inhibitory interneurons too, and enhance their inhibitory activity
4. total = partial suppression of pain perception

Question 9

Describe the spinothalamic pathway stage in pain transmission.

Answer 9

1. Along the spinothalamic pathway, there are branches to the limbic system and hypothalamus
2. These allow pain to be accompanied by emotional distress + autonomic reactions (nausea, vomiting, sweating)

Question 10

Describe the descending modulation stage of pain transmission.

Answer 10

1. Many brainstem areas involved
2. Endogenous opioids activate opioid receptors, thus inhibiting VGCCs and opening K+ channels
3. Leads to hyperpolarisation > analgesia

Question 11

What kind of fibers transmit pain?

Answer 11

1. Myelinated A-delta fibers = sharp, well-localised primary pain
2. Unmyelinated C-fibers = dull, poorly-localised secondary pain