title: Supraspinal mu 2-opioid receptors mediate spinal/supraspinal morphine synergy.
abstract: TRIMU-5 (Tyr-D-Ala-Gly-NHC2H4CH(CH3)2) is a potent mu 2-opioid agonist/mu 1-opioid antagonist. A supraspinal dose (0.5 micrograms i.c.v.) of TRIMU-5 which is not analgesic when given alone antagonizes the analgesia produced by intracerebroventricular (i.c.v.) morphine, a mu 1 action. In contrast, in a synergy model consisting of the simultaneous administration of intrathecal morphine (0.1 micrograms) with multiple doses of i.c.v. morphine, the same supraspinal TRIMU-5 dose (0.5 micrograms i.c.v.) enhances analgesia. Supraspinal TRIMU-5 also potentiates spinal morphine directly, shifting its dose-response to the left. These results imply that within the brainstem mu 1 receptors mediate supraspinal analgesia while mu 2 receptors mediate the synergy with spinal mu systems.
authors.affiliation: Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: C G
authors.initials: CG
authors.lastname: Pick
authors.forename: B
authors.initials: B
authors.lastname: Roques
authors.forename: G
authors.initials: G
authors.lastname: Gacel
authors.forename: G W
authors.initials: GW
authors.lastname: Pasternak
mesh_terms: D000698:Analgesia; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000502:physiology*
chemical_list: D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D009020:Morphine; C076955:TRIMU 5