title: The antinociceptive efficacy of morphine, metamizol, or their combination in an experimental rat model with different levels of inflammatory pain.
abstract: The purpose of this work was to evaluate the antinociceptive efficacy of an optimal morphine and metamizol combination on different levels of nociception (levels I, II, and III) using the "Pain-induced functional impairment model in the rat". The effect of acetylsalicylic acid was examined as a reference drug at the same levels of nociception. The antinociceptive effects produced by morphine (3.2 mg/kg s.c.) and metamizol (177.8 mg/kg s.c.) were studied either individually or in combination. The antinociceptive efficacies were expressed as either areas under the curve (AUCs), maximum effects as functionality index in percent of the time course, or the antinociceptive effects produced at 2 h after administration. Unlike morphine, the antinociceptive effects of acetylsalicylic acid decreased with increasing intensity of nociception. In summary, the analysis of antinociceptive efficacies produced by the co-administration of these drugs for different levels of nociception revealed that co-administration provided potentiated and better antinociceptive coverage throughout our observation time than did the individual drugs or the expected theoretical sum (using AUC or effects after 2 h). This is the first study to demonstrate that an optimal morphine and metamizol combination is able to produce potentiation of antinociceptive effects during intense pain.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Sede Sur, México D.F., México. flopez@cinvestav.mx
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: López-Muñoz
authors.forename: Beatriz
authors.initials: B
authors.lastname: Godínez-Chaparro
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Huerta-Cruz
authors.forename: Uriah
authors.initials: U
authors.lastname: Guevara-López
authors.forename: Adriana Miriam
authors.initials: AM
authors.lastname: Domínguez-Ramírez
authors.forename: Alma Rosa
authors.initials: AR
authors.lastname: Cortés-Arroyo
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D004177:Dipyrone / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014527:Uric Acid; D004177:Dipyrone; D009020:Morphine; D001241:Aspirin