Evaluation of Antinociceptive Effect of Pregabalin in Mice and its Combination with Tramadol using Tail Flick Test

Abstract

The development of combination therapy is a coherent approach in severe pain treatment. The present study investigated the antinociceptive effect of pregabalin alone and in combination with tramadol in acute pain modeling. Therefore, three groups of male mice received either pregabalin (1 to 400 mg/Kg), tramadol (10 to 80 mg/Kg) or their combination intraperitoneally. Then latency time, maximum possible effect (%MPE) and area under curve (AUC) were calculated in tail flick test. The antinociceptive indexes were significantly increasedin10, 100 and 200 mg/kg ofpregabalin while tramadol showed dose-dependentantinociception (effective dose 50% was 54 to 79 mg/Kg). The antinociceptive effect of 100 mg/Kg of pregabalin (%MPE = 35±4%) was similar to that of 50 mg/Kg of tramadol. The combination of non-analgesic doses (10 mg/Kg) of tramadol and pregabalin did not increase %MPE and AUC, but the co-administration of 30 mg/Kg of tramadol with pregabalin (10 mg/Kg) increased all antinociceptive indexes significantly compared to the controls and with each drug alone. In conclusion, pregabalin showed a comparable antinociceptive effect to tramadol. The increase in analgesic effect was observed after the combination of low analgesic doses of tramadol with pregabalin, while the combination of non-analgesic doses of each drug reversed the interaction to antagonism. Therefore to increase the analgesic effect in pain management, more attention should be paid to respecting right proportion of drug combination. Further studies that specify the mechanism(s) and statement of interaction are needed to expand these findings to clinical applications.