Exogenous neuregulin-1 attenuates STZ-induced diabetic peripheral neuropathic pain in rats.

Wuhan University, China ,Fang Zhou,Kang Liu,Qin Zhou,Zhongyuan Xia

doi:10.1590/s0102-865020170104

Abstract

To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Male SD rats were randomly divided into control group, diabetic group, NRG1 intervention group. After STZ-induced 2 weeks, NRG1 intervention daily for consecutive 7 days. 4 weeks after NRG1 intervention, both the mechanical withdrawal threshold and the morphological changes of the dorsal root ganglion and sural nerve were observed. Meanwhile, the expression of NGF, IL-1β, TNF-α in spinal cord were determined. Compared with the diabetic group, NRG1 treatment improved the mechanical withdrawal threshold in diabetic rats, pathological changes of dorsal root ganglion and sural nerve were alleviated by NRG1 treatment with electron microscopy imagine. Moreover, compared with the control group, the expression of NGF was significantly decreased and the production of IL-1β, TNF-α were markedly induced in diabetic group. Furthermore, NRG1 treatment could normalized the above effect as compared to diabetic group. NRG1 exerted positive effects on the behavioral and pathological changes of rats with STZ-induced diabetic neuropathic pain, the underlying mechanism might be related to the promotion of NGF excretion and the inhibition of inflammatory cytokines excretion.

Highlights

Diabetic peripheral neuropathic pain (DNP) is a common microvascular complication of diabetes mellitus, more than 50% of diabetic patients are suffered from this painful molestation[1], it can severely affect patients’ daily lives
To investigate the effect of NRG1 on diabetic neuropathy pain, we performed experiments two weeks after STZ injection, in which NRG1 was i.v. administered to rats for 7days
Previous evidences showed that Nerve growth factor (NGF) played a significant role in the pathogenesis of diabetic polyneuropathy, and itself had been considered an option for the treatment of diabetic peripheral pain[12]

Summary

Introduction

Diabetic peripheral neuropathic pain (DNP) is a common microvascular complication of diabetes mellitus, more than 50% of diabetic patients are suffered from this painful molestation[1], it can severely affect patients’ daily lives. There are several acceptable pathogenetic factors which can induce diabetic neuropathy pain, including polyalcohol pathway, non-enzymatic protein glycosylation, abnormal lipid metabolism ,the deficiency of neurotrophic factor, oxygen-free radical damage and so on. This painful molestation is extremely difficult to prevent and treat. NRG1 can regulate multiple aspects of SC differentiation including the survival of SC precursors, proliferation, motility, axon ensheathment and myelination[6,7], it can promote neuronal regeneration and differentiation in the peripheral nervous system by expressing neurotrophic factors including NGF. Though a substantial body of evidence suggests that NRG1 plays a key role in the recovery of nerve injury, but whether modulating NRG1 function can prevent and cure DNP remains unclear

Methods

Results

Conclusion