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

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 ED₅₀ values 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.