The mu opiate receptor is responsible for descending pain inhibition originating in the periaqueductal gray region of the rat brain.
Opiate agonists exhibiting selectivity for mu, kappa, sigma, and delta opiate receptors were microinjected into the periaqueductal gray region (PAG) of the brain of rats to determine the receptor subtype(s) associated with the initiation of descending pain inhibition. The spinally organized, heat nociceptive tail-flick reflex was used to detect analgesia. Only morphine (mu) and [D-Ala2,D-Leu5]enkephalin (DADLE) (delta greater than mu) produced analgesia. However, both drugs appeared to be acting through the mu (morphine) receptor, since: (1) the action of DADLE was not inhibited by delta receptor antagonists, (2) a more highly selective delta agonist [D-Pen2,D-Pen5]enkephalin was ineffective and (3) agonists selective at other non-mu receptor sites (ethylketocyclazocine and U50,488H for kappa; n-allylnormetazocine for sigma) were also ineffective. It appeared that DADLE might be acting as a partial agonist at the morphine receptor in the PAG. The peptide was an agonist with low efficacy, and when a maximally effective dose of the peptide was administered simultaneously with morphine antagonism was observed. Ethylketocyclazocine and n-allylnormetazocine were also found to antagonize morphine, an observation that is consistent with the suggestion that they may act as mu receptor antagonists in addition to their agonistic action at kappa and sigma receptors, respectively. Thus, mu receptors appear to be responsible for the spinopetal analgesia from the PAG of the rat.
Smith
D J
DJ
Department of Anesthesiology, West Virginia University Medical Center, Morgantown 26506.
Perrotti
J M
JM
Crisp
T
T
Cabral
M E
ME
Long
J T
JT
Scalzitti
J M
JM
D000818:Animals; D001921:Brain / Q000502:physiology*; D004347:Drug Interactions; D004723:Endorphins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009294:Narcotics / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu
D004723:Endorphins; D009294:Narcotics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu