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01.01.2016 | Original Article

Hyperexcitability and sensitization of sodium channels of dorsal root ganglion neurons in a rat model of lumber disc herniation

verfasst von: Jun Yan, Kang Zou, Xiaofeng Liu, Shufen Hu, Qianliang Wang, Xiuhua Miao, Hong-Yan Zhu, Youlang Zhou, Guang-Yin Xu

Erschienen in: European Spine Journal | Ausgabe 1/2016

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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.

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Titel: Hyperexcitability and sensitization of sodium channels of dorsal root ganglion neurons in a rat model of lumber disc herniation
verfasst von: Jun Yan
Kang Zou
Xiaofeng Liu
Shufen Hu
Qianliang Wang
Xiuhua Miao
Hong-Yan Zhu
Youlang Zhou
Guang-Yin Xu
Publikationsdatum: 01.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: European Spine Journal / Ausgabe 1/2016
Print ISSN: 0940-6719
Elektronische ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-015-4171-z

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Hyperexcitability and sensitization of sodium channels of dorsal root ganglion neurons in a rat model of lumber disc herniation