Analgesia physiology

Question 1

What 2 things can stimulate the peri-aqueductal grey?

Answer 1

Electrical stimulation

Opioids - endogenous e.g. enkephalins, or exogenous e.g. opiates

Question 2

What does stimulation of the peri-aqueductal grey cause?

How does this happen?

Answer 2

Profound analgesia

1 - It stimulates the nucleus raphe magnus, which then inhibits nociceptive transmission in the dorsal horn (laminae I and II) through 5-HT and Enkephalin axons

2 - It stimulates the Locus Coeruleus which inhibits nociceptive transmission in the dorsal horn of the spinal cord via NA axons

(both sets of axons project via the dorsolateral funiculus)

Question 3

How do opioid receptors work?

Answer 3

They are all GPCR which signal preferentially to Gi/Go. This inhibits opening of voltage-gated Ca2+ channels, opens K+ channels, and inhibits adenylyl cyclase - all of which suppresses EPSP

Question 4

3 types of opioid receptor?

Role of each of them?

Answer 4

Mu - responsible for most of the analgesic actions of opioids

Delta - contributes to analgesia but is also a pro-convulsant

Kappa - contributes to analgesia but associated with sedation, dysphoria and hallucinations

Question 5

Resp side effects of opiates? (1)

Answer 5

Apnoea

Question 6

CVS side effects of opiates? (1)

Answer 6

Orthostatic hypertension

Question 7

GI side effects of opiates? (3)

Answer 7

N&V
Constipation
Increased intrabiliary pressure

Question 8

CNS side effects of opiates? (5)

Answer 8

Confusion
Euphoria/Dysphoria
Hallucinations
Dizziness
Myoclonus
Hyperalgesia (chronic use)

Question 9

How do opioids cause excitation of the peri-aqueductal grey, therefore causing analgesia?

Answer 9

They inhibit the inhibitory GABAergic neurones normally working on PAG, i.e. disinhibiton - allowing the PAG to fire without inhibition to cause analgesia