title: The Antinociceptive Effect of a Tapentadol-Ketorolac Combination in a Mouse Model of Trigeminal Pain is Mediated by Opioid Receptors and ATP-Sensitive K+Channels.
abstract: Preclinical Research The aim of the present study was to evaluate the antinoceptive interaction between the opioid analgesic, tapentadol, and the NSAID, ketorolac, in the mouse orofacial formalin test. Tapentadol or ketorolac were administered ip 15 min before orofacial formalin injection. The effect of the individual drugs was used to calculate their ED50values and different proportions (tapentadol-ketorolac in 1:1, 3:1, and 1:3) were assayed in the orofacial test using isobolographic analysis and interaction index to evaluate the interaction between the drugs. The combination showed antinociceptive synergistic and additive effects in the first and second phase of the orofacial formalin test. Naloxone and glibenclamide were used to evaluate the possible mechanisms of action and both partially reversed the antinociception produced by the tapentadol-ketorolac combination. These data suggest that the mixture of tapentadol and ketorolac produces additive or synergistic interactions via opioid receptors and ATP-sensitive K+channels in the orofacial formalin-induced nociception model in mice. Drug Dev Res 78 : 63-70, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Departamento de Farmacología, Facultad de Odontología, Universidad Autónoma de Baja California, Mexicali, México.
authors.forename: Israel
authors.initials: I
authors.lastname: Barreras-Espinoza
authors.affiliation: Departamento de Farmacología, Facultad de Odontología, Universidad Autónoma de Baja California, Mexicali, México.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Soto-Zambrano
authors.affiliation: Departamento de Farmacología, Facultad de Odontología, Universidad Autónoma de Baja California, Mexicali, México.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Serafín-Higuera
authors.affiliation: Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, México.
authors.forename: Ramón
authors.initials: R
authors.lastname: Zapata-Morales
authors.affiliation: Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, México.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Alonso-Castro
authors.affiliation: Departamento de Investigación, Universidad de la República (UDELAR), Montevideo, Uruguay.
authors.forename: Ronell
authors.initials: R
authors.lastname: Bologna-Molina
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Cinvestav, Sede Sur, Ciudad de México, México.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
authors.affiliation: Departamento de Farmacología, Facultad de Odontología, Universidad Autónoma de Baja California, Mexicali, México.|Departamento de Investigación, Escuela de Odontología, Universidad Cuauhtémoc, San Luis Potosí, México.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Isiordia-Espinoza
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005157:Facial Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005557:Formaldehyde / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D054086:KATP Channels / Q000378:metabolism*; D020910:Ketorolac / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D010636:Phenols / Q000008:administration & dosage* / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism*; D000077432:Tapentadol
chemical_list: D000700:Analgesics; D054086:KATP Channels; D010636:Phenols; D011957:Receptors, Opioid; D005557:Formaldehyde; D000077432:Tapentadol; D020910:Ketorolac
keywords: ATP-sensitive K+ channels; ketorolac; opioid receptors; synergism; tapentadol