2016B12 Explain the mechanisms by which intravenous morphine produces analgesia.
Your answer should focus on the location and function of mu opioid receptors.

 

List:

·      Cellular effects

·      Supraspinal

·      Spinal

·      Peripheral

·      Complication of analgesia: opioid-induced hyperalgaesia and tolerance

 

Morphine’s cellular effects:

Signalling cascade

Effects

·         ↓cAMP

·         ↓VDCC activation

·         ↑K+ efflux -> hyperpolarisation

 

Supraspinal analgesia:

Receptor

Mu mostly (K and N/OFQ may be pro-nociceptive)

Locations

·  Brainstem: peri-aqueductal grey matter, rostral ventromedial medulla, nucleus raphe magnus

·  Other: thalamus, hypothalamus, cortex

Effects of opioids

·  ↑Descending modulation

·  Central effects

Diagramme

Rostral ventromedial medulla cells:

·  Note many other ascending/descending inputs/outputs

·  Note noradrenaline is anti-nociceptive; serotonin is both pro- and anti-nociceptive

 

Spinal analgesia:

Receptor

·  M, K, D

Location

·  Dorsal horn, especially layer 2

·  Major: pre-synaptic = 1° afferent = nociceptor

·  Minor: post-synaptic = 2° afferent = projection neuron (nociceptive specific or wide dynamic range)

Effect

·  ↓Ascending nociceptive signal

·  No direct effect on glutamatergic transmission; ineffective for chronic or neuropathic pain

Diagramme

 

Peripheral analgesia:

Receptor

·  M

Location

·  Peripheral nerves

Effect

·  Unclear

 

Complications of analgesia:

Tolerance

·   ↓Duration then ↓intensity of effect of a given drug dose with long term use

·   Occurs over days-weeks

·   Multiple causes: e.g. downregulation of receptors, upregulation of cAMP

Hyperalgaesia

·   ↑Pain with chronic opioid use; including hyperalgaesia and allodynia

·   Multiple causes: ↑NMDA activation, descending facilitation, receptor dysfunction (Gi -> quasi Gs)

 

 

 

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