Abstract
Background
Morphine and fentanyl are two of the most commonly used opioids to treat pain. Although both opioids produce antinociception by binding to mu‐opioid receptors (MOR), they appear to act via distinct signaling pathways.
Objective
This study will reveal whether differences in morphine and fentanyl antinociception are the result of selective activation of G‐protein signaling and/or selective activation of pre‐ or postsynaptic MORs.
Methods
The contribution of each mechanism to morphine and fentanyl antinociception was assessed by microinjecting drugs to alter G‐protein signaling or block potassium channels linked to pre‐ and post‐synaptic MORs in the ventrolateral periaqueductal gray (PAG) of male Sprague‐Dawley rats.
Results
Both morphine and fentanyl produced a dose dependent antinociception when microinjected into the PAG. Enhancement of intracellular G‐protein signaling by microinjection of the Regulator of G‐protein Signaling 4 (RGS4) antagonist CCG‐63802 into the PAG enhanced the antinociceptive potency of morphine, but not fentanyl. Microinjection of α‐dendrotoxin into the PAG to block MOR activation of presynaptic Kv + channels caused a significant rightward shift in the dose‐response curve of both morphine and fentanyl. Microinjection of tertiapin‐Q to block MOR activation of post‐synaptic GIRK channels caused a larger shift in the dose‐response curve for fentanyl than morphine antinociception.
Conclusions
These findings reveal different PAG signaling mechanisms for morphine and fentanyl antinociception. In contrast to fentanyl, the antinociceptive effects of morphine are mediated by G‐protein signaling primarily activated by presynaptic MORs.
from Wiley: European Journal of Pain: Table of Contents https://ift.tt/34LScbz
via IFTTT
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