期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 83, 期 3, 页码 420-427出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2006.03.002
关键词
gabapentin; ODQ; L-NAME; KT-5823; glibenclamide; tolbutamide; charybdotoxin; antinociception; K+ channel; formalin test
The effect of modulators of the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway on the local peripheral antinociceptive action induced by gabapentin was assessed in the rat 1% formalin test. Local peripheral administration of gabapentin produced a dose-dependent antinociception in the second phase of the test. Gabapentin-induced antinociception was due to a local action as its administration in the contralateral paw was ineffective. Local peripheral pretreatment of the paws with N-G-L-vitro-arginine methyl ester (L-NAME, a nitric oxide synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-alpha)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) and KT-5823 (a protein kinase G inhibitor) dose-dependently reduced gabapentin-induced antinociception. Likewise, glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), 4-aminopyridine or tetraethylammonium (non-selective inward rectifier K+ channel inhibitors) or charybdotoxin (large-conductance Ca2+-activated-K+ channel blocker), but not apamin (small-conductance Ca2+-activated-K+ channel blocker) or naloxone (opioid receptor antagonist), reduced the antinociception induced by gabapentin. Our data suggest that gabapentin could activate the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway in order to produce its peripheral antinociceptive effect in the rat 1% formalin test. (c) 2006 Elsevier Inc. All rights reserved.
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