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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on May 18, 2005; DOI: 10.1124/jpet.105.087130

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Received for publication April 5, 2005.
Revised May 12, 2005.
Accepted for publication May 12, 2005.

Antianalgesia: stereo-selective action of dextro-morphine and levo-morphine on glia in the mouse spinal cord

Hsiang-En Wu 1, Jonathan Thompson 1, Han-Sen Sun 1, Maia Terashvili 1, Leon F Tseng 1*

1 Medical College of Wisconsin

* Address correspondence to: E-mail: ltseng{at}post.its.mcw.edu

Abstract

Abstract: We have previously demonstrated that the naturally occurring levo-morphine at a sub-analgesic picomolar dose pretreated intrathecally (i.t.) induces antianalgesia against levo-morphine-produced antinociception. We now report that the synthetic stereo-enantiomer dextro-morphine, even at an extremely low femtomolar dose, induces antianalgesia against levo-morphine-produced antinociception using the tail-flick (TF) test in male CD-1 mice. Intrathecal pretreatment with dextro-morphine (33 fmol) time-dependently attenuated the i.t. levo-morphine-produced TF inhibition for 4 h and returned to the preinjection control level at 24 h. Intrathecal pretreatment with dextro-morphine (0.3-33 fmol), which injected alone did not affect the baseline TF latency, dose-dependently attenuated the TF inhibition produced by i.t.-administered levo-morphine (3.0 nmol). The ED50 value for dextro-morphine to induce antianalgesia was estimated to be 1.07 fmol, which is 71,000-fold more potent than the ED50 value of levo-morphine, indicating the high stereoselective action of dextro-morphine over levo-morphine for the induction of antianalgesia. Like levo-morphine, the dextro-morphine-induced antianalgesia against levo-morphine-produced TF inhibition was dose-dependently blocked by the non-opioid dextro-naloxone and by its stereo-enantiomer levo-naloxone, a non-selective µ-opioid receptor antagonist. The antianalgesia induced by both levo-morphine and dextro-morphine is reversed by the pretreatment with the glial inhibitor propentofylline (3.3-65 nmol), indicating that the antianalgesia is mediated by glial stimulation. The findings strongly indicate that the antianalgesia induced by both levo-morphine and dextro-morphine is mediated by the stimulation of a novel non-opioid receptor on glial cells.


Key words: analgesia, antianalgesia, glia, mouse, opioid, spinal cord


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