TY - JOUR
T1 - Supraspinal μ2-opioid receptors mediate spinal/supraspinal morphine synergy
AU - Pick, Chaim G.
AU - Roques, Bernard
AU - Gacel, Gilles
AU - Pasternak, Gavril W.
PY - 1992/9/22
Y1 - 1992/9/22
N2 - TRIMU-5 (Tyr-D-Ala-Gly-NHC2H4CH(CH3)2) is a potent μ2-opioid agonist/μ1-opioid antagonist. A supraspinal dose (0.5 μg i.c.v.) of TRIMU-5 which is not analgesic when given alone antagonizes the analgesia produced by intracerebroventricular (i.c.v.) morphine, a μ1 action. In contrast, in a synergy model consisting of the simultaneous administration of intrathecal morphine (0.1 μg) with multiple doses of i.c.v. morphine, the same supraspinal TRIMU-5 dose (0.5 μg 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 μ1 receptors mediate supraspinal analgesia while μ2 receptors mediate the synergy with spinal μ systems.
AB - TRIMU-5 (Tyr-D-Ala-Gly-NHC2H4CH(CH3)2) is a potent μ2-opioid agonist/μ1-opioid antagonist. A supraspinal dose (0.5 μg i.c.v.) of TRIMU-5 which is not analgesic when given alone antagonizes the analgesia produced by intracerebroventricular (i.c.v.) morphine, a μ1 action. In contrast, in a synergy model consisting of the simultaneous administration of intrathecal morphine (0.1 μg) with multiple doses of i.c.v. morphine, the same supraspinal TRIMU-5 dose (0.5 μg 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 μ1 receptors mediate supraspinal analgesia while μ2 receptors mediate the synergy with spinal μ systems.
KW - Analgesia
KW - Morphine
KW - μ-Opioid receptors
UR - http://www.scopus.com/inward/record.url?scp=0026658495&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(92)90761-R
DO - 10.1016/0014-2999(92)90761-R
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AN - SCOPUS:0026658495
SN - 0014-2999
VL - 220
SP - 275
EP - 277
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -