Comparison of antinociceptive effect of the antiepileptic drug gabapentin to that of various dosage combinations of gabapentin with lamotrigine and topiramate in mice and rats

Introduction: Newer anticonvulsants have a neuromodulatory effect on pain perception mechanisms in a hyperexcitable and damaged nervous system. Aim: This study was designed to study the analgesic effects of gabapentin alone and in combination with lamotrigine and topiramate in experimental pain models. Materials and Methods: Adult albino mice (n= 490) weighing 20-30 g and rats (n= 130) weighing 100-200 g were injected intraperitoneally with gabapentin, lamotrigine, and topiramate alone and in different dose combinations. The hot- plate method, tail- flick method, capsaicin- induced mechanical hyperalgesia, and formalin assay were used to assess the antinociceptive effects. Results: Of the three antiepileptic drugs, when given separately, gabapentin was more efficacious than either topiramate or lamotrigine in all the pain models. Combination of 25 mg/kg gabapentin with 25 mg/ kg topiramate was more efficacious (P<. 05) than 50 mg/kg gabapentin alone in the capsaicin- induced mechanical hyperalgesia test. Similarly, 50 mg/kg gabapentin with 50 mg/kg topiramate or 5 mg/kg lamotrigine was more efficacious ( P<. 05) than 50 or 100 mg/kg gabapentin alone in late-phase formalin-induced behaviors. Conclusions: Combination of gabapentin with either lamotrigine or topiramate produced better results than gabapentin alone in capsaicin-induced mechanical hyperalgesia test and in late-phase formalin-induced behaviors.