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

Abstract

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.

Comparative animal study of the antinociceptive efficacy of lamotrigine and gabapentin for the management of pain

“…This observation is similar to others that indicated the lack of GBP effect in different types of measurements of normal transient nociceptive signaling (11,15,21). It is known that GBP has no effect on normal fiber activity, but inhibits the discharge activity associated with nerve injury, lesions that are present in neuropathic pain (11,20).…”

“…However, GBP and pregabalin, have been reported to be efficient in certain types of cancer-related pain (10) or experimental nociception (13,24). Previous studies noticed that GBP reduced thermal and mechanical responses in different types of hyperalgesia (chemical or inflammatory pain) (7,11,13,21), suggesting that GBP is rather an antihyperalgesic drug than an antinociceptive drug.…”

“…Both investigated anticonvulsants decreased the hot plate response, but the effect is more pronounced for LTG, as it is noticed at different doses. The previous studies mentioned different results for LTG, with low efficacy in acute nociceptive pain (15,21). Antinociceptive effect of LTG in models of acute pain evoked by PGE 2 (16) or capsaicin (14) were reported.…”

“…Antiepileptic drugs act through a different mechanism in pain relief: potentiation of GABA transmission, reduction of glutamate transmission and blockade of different types of voltage-gated channels (21). The complexity of the underlying mechanisms is translated by the variable success to overcome pain (1,33).…”

“…By stabilizing the neuronal membrane, LTG prevents the release of excitatory mediators, inhibiting the sustained neuronal firing (21,22). In different pain models, LTG was shown to be the most potent drug due to its analgesic effects and mechanism of action (25,28,30).…”