Supraspinal μ2-opioid receptors mediate spinal/supraspinal morphine synergy

Chaim G. Pick; Bernard Roques; Gilles Gacel; Gavril W. Pasternak

doi:10.1016/0014-2999(92)90761-R

Supraspinal μ₂-opioid receptors mediate spinal/supraspinal morphine synergy

Chaim G. Pick, Bernard Roques, Gilles Gacel, Gavril W. Pasternak^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	275-277
Number of pages	3
Journal	European Journal of Pharmacology
Volume	220
Issue number	2-3
DOIs	https://doi.org/10.1016/0014-2999(92)90761-R
State	Published - 22 Sep 1992
Externally published	Yes

Keywords

Analgesia
Morphine
μ-Opioid receptors

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10.1016/0014-2999(92)90761-R

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title = "Supraspinal μ2-opioid receptors mediate spinal/supraspinal morphine synergy",

abstract = "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.",

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author = "Pick, {Chaim G.} and Bernard Roques and Gilles Gacel and Pasternak, {Gavril W.}",

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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

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Supraspinal μ₂-opioid receptors mediate spinal/supraspinal morphine synergy

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