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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 <jats:italic>\u03b2<\/jats:italic>-synthetase (CBS) in sensitization of VGSCs in a previously validated rat model of LDH. Here we showed that inhibition of CBS activity by <jats:italic>O<\/jats:italic>-(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 V<jats:sub>1\/2<\/jats:sub> of the inactivation curve, of hindpaw innervating DRG neurons, which is retrogradely labeled by DiI. <jats:italic>In vitro<\/jats:italic> incubation of AOAA did not alter the excitability of acutely isolated DRG neurons. Furthermore, CBS was colocalized with Na<jats:sub>V<\/jats:sub>1.7 and Na<jats:sub>V<\/jats:sub>1.8 in hindpaw-innervating DRG neurons. Treatment of AOAA markedly suppressed expression of Na<jats:sub>V<\/jats:sub>1.7 and Na<jats:sub>V<\/jats:sub>1.8 in DRGs of LDH rats. These data suggest that targeting the CBS-H<jats:sub>2<\/jats:sub>S signaling at the DRG level might represent a novel therapeutic strategy for chronic pain relief in patients with LDH.<\/jats:p>","DOI":"10.1038\/srep38188","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T10:43:29Z","timestamp":1480589009000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of cystathionine \u03b2-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation"],"prefix":"10.1038","volume":"6","author":[{"given":"Jun","family":"Yan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shufen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuhua","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan Ping","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang-Yin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,12,1]]},"reference":[{"key":"BFsrep38188_CR1","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/S0304-3959(03)00222-7","volume":"105","author":"SX Hou","year":"2003","unstructured":"Hou, S. 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