• Qingying Liu, Wen Chen, Xiaocen Fan, Jiaxin Wang, Su Fu, Shuang Cui, Feifei Liao, Jie Cai, Xinhong Wang, Yanhua Huang, Li Su, Lijun Zhong, Ming Yi, Fengyu Liu, and You Wan.
• Neuroscience Research Institute, Peking University, Beijing 100083, China; Department of Pain Management, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, China.
• Exp. Neurol. 2019 Jul 1; 317: 226-243.

AbstractThe T-type calcium channels Cav3.2, one of the low voltage-activated (LVA) calcium channels, have been found to play important roles in the neuronal excitability. Recently, we and others have demonstrated that accumulation of Cav3.2 channels in the dorsal root ganglion (DRG) neurons and sensory nerves contributes to neuropathic pain after peripheral nerve injury. In the present study, we aimed to further investigate the regulation of Cav3.2 channels by interleukin-6 (IL-6) in DRG neurons in neuropathic pain rats after spinal nerve ligation (SNL). The results showed that Cav3.2 channel protein expression in L5 DRG neurons was upregulated and blockade of this channel decreased the hyperexcitability of DRG neurons and mechanical allodynia in SNL neuropathic pain rats. Furthermore, inhibition of IL-6 trans-signaling reduced the upregulation of Cav3.2 T-type channel induced by FIL-6 (a fusion protein of IL-6 and sIL-6R) in primary cultured DRG neurons in vitro. In vivo, inhibition of IL-6 trans-signaling reversed the upregulation of Cav3.2, reduced the hyperexcitability of L5 DRG neurons and alleviated mechanical allodynia in SNL rats. Our results suggest that IL-6 upregulates Cav3.2 T-type channels expression and function through the IL-6/sIL-6R trans-signaling pathway in DRG neurons, thus contributes to the development of neuropathic pain in SNL rats.Copyright © 2019 Elsevier Inc. All rights reserved.

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