期刊
NEUROSCIENCE
卷 402, 期 -, 页码 51-65出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2019.01.012
关键词
radicular pain; spontaneous activity; cytokine; sympathetic nervous system; sensory neuron; inflammation
资金
- National Institute of Neurological Disorders and Stroke [NS045594, NS055860]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA [AR068989]
Low back pain is a common cause of chronic pain and disability. It is modeled in rodents by chronically compressing the lumbar dorsal root ganglia (DRG) with small metal rods, resulting in ipsilateral mechanical and cold hypersensitivity, and hyperexcitability of sensory neurons. Sodium channels are implicated in this hyperexcitability, but the responsible isoforms are unknown. In this study, we used siRNA-mediated knockdown of the pore-forming Na(V)1.6 and regulatory Na-V beta 4 sodium channel isoforms that have been previously implicated in a different model of low back pain caused by locally inflaming the L5 DRG. Knockdown of either subunit markedly reduced spontaneous pain and mechanical and cold hypersensitivity induced by DRG compression, and reduced spontaneous activity and hyperexcitability of sensory neurons with action potentials <1.5 msec (predominately cells with myelinated axons, based on conduction velocities measured in a subset of cells) 4 days after DRG compression. These results were similar to those previously obtained in the DRG inflammation model and some neuropathic pain models, in which sensory neurons other than nociceptors seem to play key roles. The cytokine profiles induced by DRG compression and DRG inflammation were also very similar, with upregulation of several type 1 pro-inflammatory cytokines and downregulation of type 2 anti-inflammatory cytokines. Surprisingly, the cytokine profile was largely unaffected by Na-V beta 4 knockdown in either model. The Na(V)1.6 channel, and the Na-V beta 4 subunit that can regulate Na(V)1.6 to enhance repetitive firing, play key roles in both models of low back pain; targeting the abnormal spontaneous activity they generate may have therapeutic value. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
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