Antinociceptive Effect of Shakuyakukanzoto, a Kampo Medicine, in Diabetic Mice

Abstract

In this study, the antinociceptive effect of shakuyakukanzoto was investigated using streptozotocin-induced diabetic mice to certify its analgesic effect on diabetic patients. Shakuyakukanzoto (0.5 and 1.0 g/kg, p.o.) significantly increased the nociceptive threshold in diabetic mice. The antinociceptive activity of shakuyakukanzoto in diabetic mice was not antagonized by β-funaltrexamine, naltrindole, or nor-binaltorphimine. The increased antinociceptive activity of (1.0 g/kg, p.o.) in diabetic mice was abolished by yohimbine (15 µg, i.t.), but not by NAN-190 (1 µg, i.t.), methysergide (15 µg, i.t.), or MDL-72222 (15 µg, i.t.). In shakuyakukanzoto diabetic mice treated with 6-hydroxydopamine (20 µg, i.t.) chemically lesioned noradrenergic pathways, shakuyakukanzoto (1.0 g/kg, p.o.) failed to exhibit an antinociceptive effect. Furthermore, the antinociceptive activity induced by norepinephrine (0.06 – 2 µg, i.t.) was markedly more potent in diabetic mice than in non-diabetic mice at the same dose. These results suggest that the antinociceptive effect of shakuyakukanzoto in diabetic mice is not mediated by the opioid systems and that this effect appears via selective activation of the spinal descending inhibitory α2-adrenergic systems without activating the serotonergic systems. The spinal α2-adrenoceptor-mediated analgesic mechanism was enhanced in diabetic mice, suggesting that shakuyakukanzoto exhibits its effect by activating the descending noradrenergic neurons. Keywords:: shakuyakukanzoto, antinociception, diabetes, descending pain inhibitory system, α2-adrenoceptor