Inhibition of cystathionine beta-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation

• Type of Material: Article
• Authors: Jun Yan, Soochow University; Shufen Hu, Soochow University; Kang Zou, Soochow University; Min Xu, Soochow University; Qianliang Wang, Soochow University; Xiuhua Miao, Soochow University; Shan Yu, Emory University; G-Y Xu, Soochow University
• Language: English
• Date: 2016-12-01
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2016.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/srep38188
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 6
• Start Page: 38188
• End Page: 38188
• Grant/Funding Information: This project is subject to the second affiliated hospital of Soochow university preponderant clinic discipline group project funding (XKQ2015008 and XKQ2015010).; This work was supported by grants from the National Natural Science Foundation of China (81230024, 81471137 and 81500952) and Priority Academic Program Development of Jiangsu Higher Education Institutions.
• Keywords: ADULT RATS; UP-REGULATION; EXPRESSION; Multidisciplinary Sciences; HYDROGEN-SULFIDE; VISCERAL HYPERSENSITIVITY; INFLAMMATORY PAIN; Science & Technology; Peripheral nervous system; SENSORY NEURONS; Ion channels in the nervous system
• Research Categories: Health Sciences, Pharmacology; Biology, Neuroscience

Abstract

The pathogenesis of pain in lumbar disc herniation (LDH) remains poorly understood. We have recently demonstrated that voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons were sensitized in a rat model of LDH. However, the detailed molecular mechanism for sensitization of VGSCs remains largely unknown. This study was designed to examine roles of the endogenous hydrogen sulfide synthesizing enzyme cystathionine β-synthetase (CBS) in sensitization of VGSCs in a previously validated rat model of LDH. Here we showed that inhibition of CBS activity by O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA) significantly attenuated pain hypersensitivity in LDH rats. Administration of AOAA also reduced neuronal hyperexcitability, suppressed the sodium current density, and right-shifted the V1/2 of the inactivation curve, of hindpaw innervating DRG neurons, which is retrogradely labeled by DiI. In vitro incubation of AOAA did not alter the excitability of acutely isolated DRG neurons. Furthermore, CBS was colocalized with NaV1.7 and NaV1.8 in hindpaw-innervating DRG neurons. Treatment of AOAA markedly suppressed expression of NaV1.7 and NaV1.8 in DRGs of LDH rats. These data suggest that targeting the CBS-H2S signaling at the DRG level might represent a novel therapeutic strategy for chronic pain relief in patients with LDH.