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Keywords:

  • gastroprotection;
  • isobolographic analysis;
  • ketorolac;
  • pain;
  • tizanidine

Abstract

Preclinical Research

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug (NSAID) effective in the treatment of moderate to severe pain. Tizanidine, an α-2-adrenoceptor agonist with myospasmolytic action, is indicated for the treatment of back pain either as monotherapy or in combination with NSAIDs. However, side effects may limit their use. As both drugs produce side effects that are dose dependent, a combination of these drugs appears in order to reduce the dose required for efficacy and, consequently, side effects. In this study, we evaluated the potential synergistic effect of these drugs in the thermal paw stimulation model and their effect on gastric ulcer production in response in the rat. Dose-response curves for ketorolac and tizanidine were constructed and from these, an ED40 value was obtained. Isobolographic analysis was carried out based on 0.5:0.5 proportions. In addition, protective effect of tizanidine against ketorolac-induced gastric damage was evaluated. A synergistic interaction in thermal hyperalgesia and gastroprotective activity was observed, suggesting a good therapeutic potential of this combination in the treatment of pain.