Examination of the interaction between peripheral lumiracoxib and opioids on the 1% formalin test in rats

Abstract

It has been shown that the association of non-steroidal anti-inflammatory drugs (NSAIDs) with opioid analgesic agents can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the aim of the present study was to examine the possible pharmacological interaction between lumiracoxib and codeine or nalbuphine at the local peripheral level in the rat using the 1% formalin test and isobolographic analysis. Lumiracoxib, codeine, nalbuphine or fixed-dose ratios lumiracoxib–codeine or lumiracoxib–nalbuphine combinations were administrated locally in the formalin-injured paw and the antinociceptive effect was evaluated using the 1% formalin test. All treatments produced a dose-dependent antinociceptive effect. ED 40 values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED 40’s for the lumiracoxib–codeine and lumiracoxib–nalbuphine combinations were 423.4 ± 31.3 μg/paw and 310.9 ± 24.2 μg/paw, respectively, being significantly higher than the actually observed experimental ED 40 values, 233.2 ± 30.9 μg/paw and 132.7 ± 11.6 μg/paw, respectively. These results correspond to a synergistic interaction between lumiracoxib and opioids at the local peripheral level, potency being about two times higher with regard to that expected from the addition of the effects of the individual drugs. Data suggest that low doses of the lumiracoxib–opioids combination can interact synergistically at the peripheral level and therefore this drug association may represent a therapeutic advantage for the clinical treatment of inflammatory pain.