title: Hyperexcitability and sensitization of sodium channels of dorsal root ganglion neurons in a rat model of lumber disc herniation.
abstract: OBJECTIVE
  Low back pain and sciatica are the most common symptoms of patients with lumbar disc herniation (LDH). The pathophysiology of lumbocrural pain and sciatica is not fully understood. The aim of the present study was to define the membrane properties and activities of voltage-gated sodium channels of dorsal root ganglion (DRG) neurons in a rat model of LDH.
  
  
  METHODS
  LDH was established by transplantation of autologous nucleus pulposus (NP) to lumbar 5 and 6 spinal nerves (L5-L6 DRG) of adult male rats. Mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL) were measured 1 day before and through 35 days after transplantation of NP. Changes in expression of VGSCs were determined by western blotting. L5-L6 DRGs neurons innervating the hindpaw were labeled with DiI and acutely dissociated for measuring excitability and sodium channel currents under whole-cell patch clamp configurations.
  
  
  RESULTS
  NP transplantation significantly reduced the PWT and PWL in association with a significant reduction in rheobase and an increase in numbers of action potentials evoked by 2X and 3X rheobase current stimulation. Voltage-gated sodium current density was significantly enhanced in L5-L6 DRG neurons from LDH rats. The inactivation curve showed a leftward shift in LDH rats while activation curve did not significantly alter. However, NP transplantation remarkably enhanced expression of NaV1.7 and NaV1.8 in L5-L6 DRGs but not in T10-12 DRGs.
  
  
  CONCLUSIONS
  These data suggest that NP application produces pain-related behavior and potentiates sodium current density of DRG neurons, which is most likely mediated by enhanced expression of NaV1.7 and NaV1.8.
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital, Soochow University, 215123, Suzhou, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital, Soochow University, 215123, Suzhou, People's Republic of China.
authors.forename: Kang
authors.initials: K
authors.lastname: Zou
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital, Soochow University, 215123, Suzhou, People's Republic of China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Laboratory for Translational Pain Medicine, Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, 215123, Suzhou, People's Republic of China.
authors.forename: Shufen
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital, Soochow University, 215123, Suzhou, People's Republic of China.
authors.forename: Qianliang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Translational Medicine, The Affiliated Zhangjiagang Hospital, Soochow University, 215600, Zhangjiagang, People's Republic of China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Miao
authors.affiliation: Center for Translational Medicine, The Affiliated Zhangjiagang Hospital, Soochow University, 215600, Zhangjiagang, People's Republic of China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Laboratory for Translational Pain Medicine, Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, 215123, Suzhou, People's Republic of China.
authors.forename: Youlang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Laboratory for Translational Pain Medicine, Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, 215123, Suzhou, People's Republic of China. guangyinxu@suda.edu.cn.|Center for Translational Medicine, The Affiliated Zhangjiagang Hospital, Soochow University, 215600, Zhangjiagang, People's Republic of China. guangyinxu@suda.edu.cn.
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Xu
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D005727:Ganglia, Spinal / Q000503:physiopathology*; D007405:Intervertebral Disc Displacement / Q000503:physiopathology*; D008159:Lumbar Vertebrae / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D061566:Voltage-Gated Sodium Channels / Q000502:physiology*
chemical_list: D061566:Voltage-Gated Sodium Channels
keywords: Dorsal root ganglion; Excitability; Lumbar disc herniation; Neuropathic pain; Voltage-gated sodium channels