Antianalgesia: stereoselective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord.
We have previously shown that the naturally occurring levo-morphine at a subanalgesic picomolar dose pretreated 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 ED(50) value for dextro-morphine to induce antianalgesia was estimated to be 1.07 fmol, which is 71,000-fold more potent than the ED(50) 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 nonopioid dextro-naloxone and its stereo-enantiomer levo-naloxone, a nonselective mu-opioid receptor antagonist. The antianalgesia induced by 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 levo-morphine and dextro-morphine is mediated by the stimulation of a novel nonopioid receptor on glial cells.
Wu
Hsiang-En
HE
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, 53226, USA.
Thompson
Jonathan
J
Sun
Han-Sen
HS
Terashvili
Maia
M
Tseng
Leon F
LF
D000698:Analgesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D013237:Stereoisomerism; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; D009270:Naloxone; C032114:propentofylline; D009020:Morphine