Participation of the components of L-arginine/nitric oxide/cGMP cascade bychemically-induced abdominal constriction in the mouse

The purpose of this study was to investigate the role of the L-arginine/nit ric oxide (NO)/cGMP pathway in p-benzoquinone-induced writhing model in mou se. L-arginine, a NO precursor, displayed antinociceptive effects at the do ses of 0.125-1.0 mg/kg. When the doses of L-arginine were increased gradual ly to 10-100 mg/kg, a dose-dependent triphasic pattern of nociception-antin ociception-nociception was obtained. The NO synthase (NOS) inhibitor, NC-ni tro-L-arginine methyl ester (L-NAME) (18.75-150 mg/kg), possessed antinocic eptive activity. Methylene blue (MB), a guanylyl cyclase and/or NOS inhibit or, (5-160 mg/kg) also produced a dose-dependent triphasic response. When L -arginine (50 mg/kg) was combined with L-NAME (75 mg/kg), L-arginine-induce d antinociception did not change significantly. Cotreatment of L-arginine w ith 5 mg/kg MB significantly decreased MB-induced antinociception and rever sed the nociception induced by 40 mg/kg MB to antinociception. It is conclu ded that the components of L-arginine/nitric oxide/cGMP cascade may partici pate in nociceptive processes both peripherally and centrally by a direct e ffect on nociceptors or by the involvement of other related pathways of noc iceptive processes induced by NO. (C) 2000 Elsevier Science Inc. All rights reserved.