Jun Yan1, Kang Zou1, Xiaofeng Liu1, Shufen Hu2, Qianliang Wang1, Xiuhua Miao3, Hong-Yan Zhu3, Youlang Zhou2, Guang-Yin Xu4,5. 1. Department of Orthopedics, The Second Affiliated Hospital, Soochow University, 215123, Suzhou, People's Republic of China. 2. 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. 3. Center for Translational Medicine, The Affiliated Zhangjiagang Hospital, Soochow University, 215600, Zhangjiagang, People's Republic of China. 4. 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. 5. Center for Translational Medicine, The Affiliated Zhangjiagang Hospital, Soochow University, 215600, Zhangjiagang, People's Republic of China. guangyinxu@suda.edu.cn.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: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. CONCLUSION: 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: Iain T Strickland; Jo C Martindale; Peter L Woodhams; Alison J Reeve; Iain P Chessell; Daniel S McQueen Journal: Eur J Pain Date: 2007-10-18 Impact factor: 3.931
Authors: Jianying Huang; Yang Yang; Peng Zhao; Monique M Gerrits; Janneke G J Hoeijmakers; Kim Bekelaar; Ingemar S J Merkies; Catharina G Faber; Sulayman D Dib-Hajj; Stephen G Waxman Journal: J Neurosci Date: 2013-08-28 Impact factor: 6.167