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 journalArticlepeer-review

23 Scopus citations


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 languageEnglish
Pages (from-to)275-277
Number of pages3
JournalEuropean Journal of Pharmacology
Issue number2-3
StatePublished - 22 Sep 1992
Externally publishedYes


FundersFunder number
National Institute on Drug AbuseR01DA007242


    • Analgesia
    • Morphine
    • μ-Opioid receptors


    Dive into the research topics of 'Supraspinal μ2-opioid receptors mediate spinal/supraspinal morphine synergy'. Together they form a unique fingerprint.

    Cite this