The Involvement of Nitric Oxide in the Analgesic Effects of Ketamine

Abstract

We investigated the contribution of NO-cyclic GMP (cGMP) pathway to the antinociceptive effects of ketamine in mice by using the nitric oxide synthase inhibitor nitro(g)-L-arginine methyl ester (L-NAME). Intraperitoneal (i.p.) (1 5 or 10 mg/kg) or intrathecal (i.th.) (10 30 or 60 mug/mouse) administration of ketamine produced dose-dependent antinociceptive effects in the acetic acid-induced writhing and formalin tests but not in the tail-flick nor in hot-plate tests. pretreatment of mice with L-NAME (10 mg/kg i.p.) which produced no antinociception on its own significantly inhibited the antinociceptive effect of ketamine (1 5 or 10 mg/kg i.p.). However L-NAME (30 mug/mouse) was given intrathecally it neither modified the antinociceptive effect of i.th. ketamine (10 3 0 or 60 mug/mouse) nor did it produce an antinociceptive effect alone. These data suggest that the activation of the NO-cGMP pathway probably at the supraspinal level but not spinal level contributes to the antinociceptive effects of ketamine. (C) 2002 Published by Elsevier Science Inc.