his 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.