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This study was designed to evaluate the possible synergistic antinociceptive interactions between diclofenac, benfotiamine, and resveratrol on acetic acid‐induced nociception in mice. Isobolographic analyses were used to define the nature of the interactions between drugs. Diclofenac, benfotiamine, or resveratrol, as well as their combinations, produced a dose‐dependent antinociceptive effect. ED30 values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED30 values for the combinations estimated from the isobolograms were 170.9±23.4, 4.9±1.0, and 173.3±11.8 mg/kg for the diclofenac+benfotiamine, diclofenac+resveratrol, or benfotiamine+resveratrol combination, respectively. These values were significantly higher than the actually observed ED30 values, which were 10.2±1.9, 0.3±0.1, and 5.3±0.8 mg/kg, respectively, indicating a synergistic interaction in the three combinations. Data indicate that low doses of the diclofenac+benfotiamine, diclofenac+resveratrol, or benfotiamine+resveratrol combination can interact synergistically to reverse acetic acid‐induced nociception and they may represent a therapeutic advantage for clinical treatment of inflammatory pain. Drug Dev Res 72: 397–404, 2011. © 2011 Wiley‐Liss, Inc.

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