Antinociceptive Interaction between Diclofenac and Statins: An Isobolographic Analysis

Export Most of the available pharmacological strategies of pain relief use drugs that have monomodal mechanisms of analgesia. However, pain treatment requires combinations of drugs with nonredundant mechanisms of action to improve pain management and reduce the adverse effects produced by high doses of individual drugs. This study aimed to investigate, through isobolographic analysis, whether statins can modify the antinociceptive effect produced by diclofenac. The above was measured by the formalin test in rats, a murine animal model of acute inflammatory pain. Animals were administered with diclofenac (0.3, 1, 3 and 10 mg/kg; p.o.), atorvastatin (1, 3, 10 and 30 mg/kg; p.o.), pravastatin (1, 3, 10 and 30 mg/kg; p.o.), rosuvastatin (1, 3, 10 and 30 mg/kg; p.o.), or calculated combinations of diclofenac with the different statins. The effective doses 30 (ED30) were calculated for diclofenac and statins, and subsequently, the isobolographic analysis of each one of the combinations was performed, thus determining their respective ED30. The experimental ED30 values of antinociception for diclofenac coadministered with atorvastatin, pravastatin, or rosuvastatin were 0.27 ± 0.01, 1.30 ± 0.08, and 0.59 ± 0.08, respectively, while the corresponding theoretical ED30 values of antinociception were 5.08 ± 0.33, 5.30 ± 0.33, and 6.64 ± 0.3, respectively, being statistically higher (P < 0.05) theoretical ED30 values than their corresponding experimental ED30 values. The above suggests that statins enhance the antinociceptive effect of diclofenac. These pharmacological combinations may help treat pain.