Comparison of analgesic potencies of mu, delta and kappa agonists locally applied to various CNS regions relevant to analgesia in rats.
Analgesic potencies of relatively selective agonists for mu, delta and kappa subtypes of opioid receptors, morphine, [D-Ala2,D-Leu5]-enkephalin (DADL) and ethylketocyclazocine (EKC), respectively, were examined with the tail-pinch test in the rat, when microinjected into the brain stem regions relevant to analgesia such as the nucleus reticularis paragigantocellularis (NRPG), nucleus raphe magnus (NRM) and periaqueductal gray matter (PAG), and into the lumbar subarachnoid space (LSS). Morphine, DADL and EKC produced dose-dependent analgesic effects at the NRPG, NRM, PAG and LSS. The ED50 values indicated that morphine was more potent than DADL at the NRPG and LSS but less at the NRM and PAG. EKC was the weakest at all the injection sites. Further, naloxone (0.1 mg/kg, s.c.) significantly antagonized the analgesic effect of morphine but not that of DADL or EKC at the NRPG. These findings suggest that mu, delta and kappa subtypes of opioid receptors mediate analgesia, and that the extent of contribution of each subtype to the production of analgesia differs among the CNS sites examined in this study.
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D016314:Ethylketocyclazocine; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; D003496:Cyclazocine