Mechanisms of opioid analgesia in the peripheral nervous system
Authors: Davis Maclean Reviewers: Heather Yong Tony Gu Yan Yu* Carlos Camara- Lemarroy* * MD at time of publication
Exposure to opioid
Natural
Naturally occurring extracted from opium poppy (e.g. morphine)
Exogenous
Opioids derived from external source
Semi-synthetics
Synthesized from natural sources (ex. heroin)
Synthetics
Entirely created via synthesis (ex. fentanyl)
Endogenous
Opioids produced naturally in the body
Released in response or in anticipation of to painful stimuli
Endorphins
Enkephalins
Dynorphins
Inhibition of adenyl cyclase
↓ conductance of presynaptic Ca2+ channels
↑ conductance of postsynaptic K+ channels
↓Activity and production of cAMP
Activation of G- protein coupled receptors
↓ neuro- transmitter release
Inhibition of postsynaptic neuron
Blockage of nerve transmission
Binding to opioid receptor subtypes in nervous tissues mu (μ), kappa (k) delta (δ) – Majority of clinically relevant analgesic effects relate to mu (μ) receptor
↓ Release of Substance P and Glutamate in the dorsal horn of spinal cord
↓ Peripheral nociceptive signaling to thalamus and other brain areas
Inhibition of pain transmission to brain
Inhibition of GABA- releasing neurons in Periaqueductal grey (PAG) area
Activation of descending inhibitory pathways from PAG
Other/Systemic Side Effects
(For complete list and mechanism see Calgary Guide – Side effects of Opioids
Abbreviations:
cAMP (cyclic Adenosine mono-phosphate) – Cellular signaling molecule
GABA (gamma-Aminobutyric acid) – Inhibitory neurotransmitter
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published March 4, 2020 on www.thecalgaryguide.com