Metamizol potentiates morphine effects on visceral pain and evoked c-Fos immunoreactivity in spinal cord.
In a model of visceral pain consisting of intraperitoneal injection of acetic acid (writhing test), simultaneous administration of subanalgesic doses of metamizol (150 mg/kg) and morphine (0.2 mg/kg) resulted in a potent analgesia (19 +/- 1 vs. 2.3 +/- 0.8 writhes; P < 0.05). While the analgesic effect of morphine (2 mg/kg) was antagonized by naloxone (1 mg/kg), the opioid antagonist did not reverse the analgesia induced by the combination of metamizol and morphine. Potentiation by metamizol was also observed as a bilateral decrease in stimulus-evoked c-Fos induction in superficial laminas (I-II) of the dorsal spinal cord after drug combination compared to single administration (66.5 +/- 2.2 vs. 80.7 +/- 4.2; P < 0.05). Conversely, the number of nuclei immunostained with an antibody that recognizes all proteins of the Fos family was not modified by the same dose combination compared to single treatment (21.1 +/- 1.3 vs. 20.2 +/- 1.2). Furthermore, in a model of somatic pain consisting of peripheral thermal stimulation of the paws, simultaneous administration of metamizol (100-250 mg/kg) and morphine (0.5 mg/kg) failed to modify flexor reflex latency.
Instituto Cajal, Consejo Superior Investigaciones Científicas, Madrid, Spain.
J
J
Taylor
B
B
Mellström
I
I
Fernaud
J R
JR
Naranjo
D019342:Acetic Acid; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D004177:Dipyrone / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D017833:Visceral Afferents / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009292:Narcotic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D009270:Naloxone; D004177:Dipyrone; D009020:Morphine; D019342:Acetic Acid