Synergistic interaction between 4-allyl-1-hydroxy-2-methoxybenzene (eugenol) and diclofenac: An isobolograpic analysis in Wistar rats

Clinical and preclinical research that contributes pain palliation has suggested that drugs favor the expected effects and minimize the adverse effects. Among the most widely used strategies is the combination of analgesic drugs among those in the same group, with those in another group of analgesics or with co-adjuvants (nonanalgesic drugs or elements of traditional medicine). This work aims to evaluate the interaction between eugenol (EUG) and diclofenac (DFC) on nociception in the presence of a noxious stimulus through the formalin test and isobolographic analysis. The results indicate that EUG, DFC, or the combination of both produce an antinociceptive effect in rodents (p ≤ 0.05). Local co-administration of EUG and DFC gave a theoretical effective dose (Z_add) 2,936.27 ± 155.33 μg/kg (p ≤ 0.05) significantly higher as compared to the effective experimental doses (Z_mix) of 866.89 ± 0.02 μg/kg in phase 1 and 292.88 ± 0.05 μg/kg in phase 2, with an interaction index of 0.29 and 0.09, respectively. These data allow concluding that the interaction derived from the joint administration of EUG and DFC, in the rodent at a local level, is synergistic.