Effect of goshajinkigan on the mechanical hypoesthesia of streptozotocin‐induced diabetic peripheral neuropathy in mice

ABSTRACT Aim Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus. While there are several reports of treatments and prevention for hyperesthesia and hyperalgesia in DPN, there are no effective treatments for hypoesthesia. In the present study, we examined some Kampo prescriptions that were effective for hypoesthesia in the later stage of DPN. Methods Male ICR mice were injected with streptozotocin and the 50% threshold for mechanical stimulation was calculated by performing a von Frey test using the left footpad of diabetic mice. Results The 50% paw withdrawal threshold increased significantly six weeks after streptozotocin (STZ) treatment, showing mechanical hypoesthesia in diabetic mice, which was significantly ameliorated after administration of goshajinkigan (GJG). Pretreatment with NG‐nitro‐L‐arginine methyl ester (L‐NAME) in diabetic mice inhibited the ameliorative effect of GJG, suggesting the possibility that the improvement in sensory reduction demonstrated by GJG resulted from increasing nitric oxide. To assess the mechanism of GJG action, we demonstrated the possibility that L‐arginine was supplied by GJG as a substrate for nitric oxide synthase (NOS). We further found that four kinds of crude drugs contributed to the ameliorative effect of GJG in the mechanical hypoesthesia in DPN. The L‐arginine content of these four crude drugs was compared in terms of the potency of the ameliorative effects on hypoesthesia and a mechanism is suggested not only for the substrate supply but also for NOS activation. Conclusion Here, we found for the first time that GJG improves the mechanical hypoesthesia in the later stage of DPN.