title: Inhibition of cystathionine β-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation.
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 V1/2of 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.
authors.affiliation: Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China.
authors.forename: Shufen
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Zou
authors.affiliation: Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Qianliang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for translational Medicine, the Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Shan Ping
authors.initials: SP
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China.|Center for translational Medicine, the Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China.
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Xu
mesh_terms: D000818:Animals; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology; D006898:Hydroxylamines / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000473:pathology; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000378:metabolism*; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats
chemical_list: D006898:Hydroxylamines; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568319:Scn10a protein, rat; C503480:Scn9a protein, rat; D003541:Cystathionine beta-Synthase