• Teresa Mixcoatl-Zecuatl, Roberto Medina-Santillán, Gerardo Reyes-García, Guadalupe C Vidal-Cantú, and Vinicio Granados-Soto.
• Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
• Eur. J. Pharmacol. 2004 Jan 26; 484 (2-3): 201-8.

AbstractThe effect of K+ channel inhibitors on the antiallodynic activity induced by spinal gabapentin was assessed in rats. Ligation of L5 and L6 spinal nerves made the rats allodynic, whereas that intrathecal administration of gabapentin (25-200 microg) reduced tactile allodynia in a dose-dependent manner. Spinal pretreatment with glibenclamide (12.5-50 microg, ATP-sensitive K+ channel inhibitor), charybdotoxin (0.01-1 ng) or apamin (0.1-3 ng, large-and small-conductance Ca2+-activated K+ channel blockers, respectively), but not margatoxin (0.01-10 ng, voltage-dependent K+ channel inhibitor), significantly prevented gabapentin-induced antiallodynia. Pinacidil (1-30 microg, K+ channel opener) significantly reduced nerve ligation-induced allodynia. Intrathecal glibenclamide (50 microg), charybdotoxin (1 ng) and apamin (3 ng), but not margatoxin (10 ng), significantly reduced pinacidil-induced antiallodynia. K+ channel inhibitors alone did not modify allodynia produced by spinal nerve ligation. Results suggest that gabapentin and pinacidil may activate Ca2+-activated and ATP-sensitive K+ channels in order to produce part of its spinal antiallodynic effect in the Chung model.

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