Antinociceptive mechanism of Gosha-jinki-gan in streptozotocin-induced diabetic animals: role of nitric oxide in the periphery.

Using streptozotocin-induced diabetic mice and rats, we evaluated the antinociceptive mechanism of Gosha-jinki-gan. The antinociceptive effect of Gosha-jinki-gan (0.3 g/kg, p.o.) in diabetic mice, as determined by the tail-pressure test, was inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME; 2, 5 mg/kg, i.p.). When L-NAME (10 microg) or methylene blue (500 microg) was topically administered to the intraplantar area of the hind paw, the region used for the paw-pressure test, the antinociceptive activity of Gosha-jinki-gan (0.3 g/kg, p.o.) in diabetic rats was decreased. These results suggested that the antinociceptive effect of Gosha-jinki-gan partly resulted from the peripheral action of increasingly produced nitric oxide.