• Eur. J. Pharmacol. · Feb 2006

    The nitric oxide-cyclic GMP-protein kinase G-K+ channel pathway participates in the antiallodynic effect of spinal gabapentin.

    • Teresa Mixcoatl-Zecuatl, Francisco J Flores-Murrieta, and Vinicio Granados-Soto.
    • Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Coapa, Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330, México, DF, Mexico.
    • Eur. J. Pharmacol. 2006 Feb 15;531(1-3):87-95.

    AbstractThe possible participation of the nitric oxide (NO)-cyclic GMP-protein kinase G (PKG) pathway on gabapentin-induced spinal antiallodynic activity was assessed in spinal nerve injured rats. Intrathecal gabapentin, diazoxide or pinacidil reduced tactile allodynia in a dose-dependent manner. Pretreatment with NG-L-nitro-arginine methyl ester (L-NAME, non-specific inhibitor of NO synthase NOS), 7-nitroindazole (neuronal NO synthase inhibitor), 1H-[1,2,4] -oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, guanylyl cyclase inhibitor) or (9S, 10R, 12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo-[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT-5823, specific PKG inhibitor), but not NG-D-nitro-arginine methyl ester (D-NAME) or okadaic acid (protein phosphatase 1 and 2 inhibitor) prevented gabapentin-induced antiallodynia. Pinacidil activity was not blocked by L-NAME, D-NAME, 7-nitroindazole, ODQ, KT-5823 or okadaic acid. Moreover, KT-5823, glibenclamide (ATP-sensitive K+ channel blocker), apamin and charybdotoxin (small- and large-conductance Ca2+-activated K+ channel blockers, respectively), but not margatoxin (voltage-gated K+ channel blocker), L-NAME, 7-nitroindazole, ODQ or okadaic acid, reduced diazoxide-induced antiallodynia. Data suggest that gabapentin-induced spinal antiallodynia could be due to activation of the NO-cyclic GMP-PKG-K+ channel pathway.

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