Journal
LIFE SCIENCES
Volume 71, Issue 7, Pages 841-853Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0024-3205(02)01765-4
Keywords
ketamine; nitric oxide; analgesia; NMDA receptors; anaesthetics; L-N-G nitro arginine methylester (L-NAME); formalin; writhing; pain; dissociative anesthesia
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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.
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