Synergistic interaction between tramadol and dipyrone in thermal paw stimulation model in the rat

Dipyrone, also known as metamizol, and tramadol are drugs that are widely used for the treatment of pain; however, side effects can limit their use. As dipyrone and tramadol produce side effects that are dose dependent, it seems appropriate to combine these drugs to reduce their dose requirements and, consequently, side effects. The purpose of this study was to evaluate whether dipyrone and tramadol produce antihyperalgesic effects in the thermal paw stimulation model in the rat, and whether there is a synergistic interaction between them. Using this model, dose-response curves were constructed for dipyrone (10-178 mg/kg, p.o.) and tramadol (1-32 mg/kg p.o.). From these curves, an ED₅₀ value was obtained and isobolographic analyses were carried out based on 1:1 and 0.6:0.4 (dipyrone:tramadol) potency ratio proportions. When the proportion was 1:1, an additive interaction was obtained, whereas the 0.6:0.4 proportion showed a synergistic interaction. These results suggest a good therapeutic potential of this combination.