Antinociceptive Effect of Gosha-jinki-gan, a Kampo Medicine, in Streptozotocin-Induced Diabetic Mice

We evaluated the antinociceptive effect of Gosha-jinki-gan, a Kampo medicine including processed Aconiti tuber, and its mechanism in streptozotocin-induced diabetic mice. Gosha-jinki-gan (0.1-1.0 g/kg, p.o.) showed a more potent antinociceptive effect in diabetic mice than in non-diabetic mice. The antinociceptive effect of Gosha-jinki-gan (0.3 g/kg, p.o.) in diabetic mice was inhibited by administration of either anti-dynorphin antiserum (5 microg, i.t.) or nor-binaltorphimine (10 mg/kg, s.c.), a kappa-opioid antagonist. The antinociceptive activity of Gosha-jinki-gan (0.3, 1.0 g/kg, p.o.) was decreased by excluding processed Aconiti tuber. Furthermore, the antinociceptive effect of processed Aconiti tuber (0.03, 0.1 g/kg, p.o.) was also shown to be enhanced in diabetic mice. These results suggest that the increased antinociceptive effect of Gosha-jinki-gan in diabetic mice is partly derived from the action of processed Aconiti tuber and that it is based on stimulation of spinal kappa-opioid receptors via dynorphin release. Gosha-jinki-gan was considered useful for treating painful diabetic neuropathy.