Role of guanylyl cyclase activation via thiamine in suppressing chemically-induced writhing in mouse

The possible role of L-arginine/nitric oxide (L-arginine/NO) pathway in the antinociceptive activity of thiamine (vitamin B-1) in p-benzoquinone-induc ed mouse writhing model was investigated. Thiamine (ED50, 0.11 mg/kg), L-ar ginine (50 mg/kg), N-G-nitro-L-arginine methyl ester (L-NAME, 75 mg/kg) and morphine (ED50: 0.13 mg/kg) displayed antinociceptions following sc. admin istrations (52.4 +/- 5.5 %, 36.8 +/- 7.7 %, 27.8 +/- 11.1 %, 66.1 +/- 3.5 % , respectively). However. methylene blue (MB, 40 mg/kg, s.c.) produced a no ciception (-32.1 +/- 9.9 %). Coadministration of B-1 with L-arginine did no t significantly change L-aminine-induced antinociception (48.9 +/- 3.7 %). Cotreatment of thiamine with L-NAME and MB significantly increased the L-NA IME-induced antinociception (53.9 +/- 3.9 %) and reversed the MB-induced no ciception to antinociception (46.0 +/- 4.2 %). L-Arginine and L-NAME-induce d antinociceptions were significantly increased (55.9 +/- 3.9 % and 61.1 +/ - 5.0 %, respectively) by morphine. MB-induced nociception significantly re versed to antinociception by the concomitant administration of morphine (41 .6 +/- 8.9 %). Thiamine and morphine coadministration displayed antinocicep tion (46.0 +/- 4.2 %). The present results suggest that thiamine could prod uce antinociception by the activation of guanylyl cyclase mediated by cycli c guanosine monophosphate (cGMP) that may trigger the possible involvement of central and/or peripheral L-arginine/NO/cGMP pathway.