Systematic Administration of B Vitamins Alleviates Diabetic Pain and Inhibits Associated Expression of P2X3 and TRPV1 in Dorsal Root Ganglion Neurons and Proinflammatory Cytokines in Spinal Cord in Rats.

Xue-Jun Song,Shan Wang,Zhong Xie,Yu Gao,Duan-Duan He

doi:10.1155/2020/3740162

Abstract

Background Treatment of diabetic neuropathic pain (DNP) continues to be a major challenge, and underlying mechanisms of DNP remain elusive. We investigated treatment effects of B vitamins on DPN- and DNP-associated alterations of neurochemical signaling in the nociceptive dorsal root ganglion (DRG) neurons and the spinal cord in rats. Methods DNP was produced in male, adult, Sprague Dawley rats by single i.p. streptozotocin (STZ). Western blot analysis and immunohistochemistry were used to analyze protein expressions in DRG and ELISA to measure the proinflammatory cytokines in the spinal cord. Behaviorally expressed DNP was determined by measuring the sensitivity of hindpaw skin to mechanical and thermal stimulation. Results There were 87.5% (77/88) rats which developed high blood glucose within 1-2 weeks following STZ injection. Of which, 70.13% (n = 54/77) animals exhibited DNP manifested as mechanical allodynia and/or thermal hyperalgesia. Intraperitoneal administration of vitamins B1/B6/B12 (100/100/2 mg/kg, one or multiple doses) significantly attenuated DNP without affecting the blood glucose. Expressions of P2X3 and TRPV1 in CGRP-positive and IB4-positive DRG neurons as well as the interleukin-1β, tumor necrosis factor-α, and nerve growth factor in the lumbar spinal cord were greatly increased in DNP rats. Such DNP-associated neurochemical alterations were also greatly suppressed by the B-vitamin treatment. Conclusions B-vitamin treatment can greatly suppress chronic DNP and DNP-associated increased activities of P2X3 and TRPV1 in DRG and the spinal proinflammatory cytokines, which may contribute to the pathogenesis of DNP. Systematic administration of B vitamins can be a strategy for DNP management in clinic.

Highlights

Diabetic neuropathic pain (DNP) is one of the most common chronic complications in patients with diabetes mellitus [1, 2]
We investigated whether VBC can regulate P2X3 and transient receptor potential vanilloid 1 (TRPV1), two important membrane proteins associated with DNP, in the dorsal root ganglion (DRG) neurons, as well as whether VBC administration can regulate mediators of inflammatory pain (IL-1β, tumor necrosis factor (TNF)-α, and nerve growth factor (NGF)) in the spinal cord
Our results demonstrated that VBC treatment can significantly attenuate thermal hyperalgesia and mechanical allodynia in STZ-induced diabetic rats and suppress the increased expression of P2X3 and TRPV1 in DRG, and the increased level of IL-1β, tumor necrosis factor-α (TNF-α), and NGF in the lumbar spinal cord, in STZ-induced diabetic rats

Summary

Introduction

Diabetic neuropathic pain (DNP) is one of the most common chronic complications in patients with diabetes mellitus [1, 2]. Pain Research and Management [11, 16]; immune dysfunction [17]; activation of ephrinBEphB receptor signaling in the spinal cord [18]; and oxidant stresses in mitochondria and endoplasmic reticulum [11, 16] Despite these efforts over the past decades, the specific cellular and molecular mechanisms underlying DNP pathogenesis remain elusive, and clinical approaches for DNP treatment are limited. Our results demonstrated that VBC treatment can significantly attenuate thermal hyperalgesia and mechanical allodynia in STZ-induced diabetic rats and suppress the increased expression of P2X3 and TRPV1 in DRG, and the increased level of IL-1β, TNF-α, and NGF in the lumbar spinal cord, in STZ-induced diabetic rats.

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Conclusion