Modulatory role of Gabapentin alone and on co-administration with Verapamile or Nimesulide in acute inflammatory condition

By Otari Kishor Vasant, Taranalli Ashok Dundappa, Shete Rajkumar Virbhadrappa, Singh Vijay Pal  and Harpallani Anand Nirmal

ABSTRACT
Gabapentin, a novel anticonvulsant drug, was found to be an effective anti-nociceptive in neuropathic pain. The effect of gabapentin has been studied in several experimental paradigms of pain particularly, neuropathic pain. Also gabapentin was shown to reduce hyperalgesia and inhibit C-fiber responses to noxious stimuli in animal models of inflammatory pain (injection of formalin or carrageenan). The present research work was therefore, focused to investigate the effect of gabapentin in acute inflammatory condition in carrageenan-induced rat paw edema. Further, the effect of gabapentin on myeloperoxidase activity, lipid peroxidation and histopathlogical changes in the rat footpad tissues were evaluated. In addition, in combination study the effect of sub-effective dose combinations of gabapentin with verapamile or nimesulide were studied in carrageenan-induced rat paw edema. Gabapentin (10, 30 & 100 mg/kg, po) was demonstrated inhibition of carrageenan-induced rat paw inflammation. Also significant inhibition of the myeloperoxidase activity, generation of lipid peroxides and morphological injury in footpad tissues, induced by carrageenan, was evident at higher dose tested. On co-administration, the sub-effective dose of nimesulide (0.5 mg/kg, po) or verapamil (2 mg/kg, po) significantly enhanced the anti-inflammatory effect of sub-effective dose of gabapentin (5 mg/kg, po) against carrageenan induced-paw edema in rats when compared to the effect per se. It was suggested that, by possibly binding to the a2d subunit, gabapentin might affect Ca2+ currents, which might modulate neurotransmitter release, neuronal excitability or release or synthesis of inflammatory mediators thereby alleviating the inflammatory conditions. In addition the results of combination study suggested that the co-administration of gabapentin with drugs acting through other transaction pathways (COX, Ca2+ etc) in inflammation might pose a beneficial effect in the clinics for the treatment inflammatory conditions.

Key words: Gabapentin; Inflammation; Myeloperoxidase; Lipid peroxidation; Calcium channel blocker; Nimesulide.

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