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Author Notes:

Correspondence and requests for materials should be addressed to G.-Y.X. (email: guangyinxu@suda.edu.cn).

J. Yan and S. Hu contributed equally to this work.

Jun Yan: Designed the experiments, analyzed data and drafted the manuscript.

Shufen Hu: Performed experiments, analyzed data, prepared figures and drafted the manuscript.

Kang Zou: Performed experiments, analyzed data, prepared figures.

Min Xu: Performed experiments and analyzed data.

Qianliang Wang: Performed experiments and analyzed data.

Xiuhua Miao: Analyzed data and prepared figures.

Shan Ping Yu: Edited the manuscript.

Guang-Yin Xu: Designed and supervised the experiments and edited the manuscript.

The authors declare no competing financial interests.

The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects:

Research Funding:

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.

This project is subject to the second affiliated hospital of Soochow university preponderant clinic discipline group project funding (XKQ2015008 and XKQ2015010).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • HYDROGEN-SULFIDE
  • SENSORY NEURONS
  • UP-REGULATION
  • VISCERAL HYPERSENSITIVITY
  • INFLAMMATORY PAIN
  • ADULT RATS
  • EXPRESSION
  • Ion channels in the nervous system
  • Peripheral nervous system

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

Tools:

Journal Title:

Scientific Reports

Volume:

Volume 6

Publisher:

, Pages 38188-38188

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© The Author(s) 2016.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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