title: p38 mitogen-activated protein kinase inhibitor SB203580 reverses the antianalgesia induced by dextro-morphine or morphine in the mouse spinal cord.
abstract: We have previously demonstrated that intrathecal pretreatment with dextro-morphine or morphine attenuates the morphine-produced antinociception. The phenomenon has been defined as antianalgesia, which is mediated by a non-opioid receptor [Wu, H., Thompson, J., Sun, H., Terashvili, M., Tseng, L.F., 2005. Antianalgesia: stereo-selective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord. J. Pharmacol. Exp. Ther. 314, 1101-1108]. To determine if p38 mitogen-activated protein kinase (MAPK) is involved in the antianalgesia, the effects of p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) on the attenuation of the morphine-produced tail-flick inhibition induced by dextro-morphine or morphine were studied in male CD-1 mice. Intrathecal pretreatment with SB203580 (24.2 nmol) reversed the attenuation of the morphine-produced tail-flick inhibition induced by dextro-morphine (33 fmol) or morphine (0.3 nmol) pretreatment. The finding indicates that the antianalgesia induced by dextro-morphine or morphine is mediated by the activation of p38 MAPK in the mouse spinal cord.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Medical Education Building, Room M4308, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Hsiang-En
authors.initials: HE
authors.lastname: Wu
authors.forename: Han-Sen
authors.initials: HS
authors.lastname: Sun
authors.forename: Caleb W
authors.initials: CW
authors.lastname: Cheng
authors.forename: Leon F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D013237:Stereoisomerism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D009020:Morphine; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580