• Ying Zang, Xin-Hua He, Wen-Jun Xin, Rui-Ping Pang, Xu-Hong Wei, Li-Jun Zhou, Yong-Yong Li, and Xian-Guo Liu.
• Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, 74 Zhongshan Rd 2, Guangzhou 510080, PR China.
• Brain Res. 2010 Dec 2;1363:151-8.

AbstractActivation of nucleus factor-kappaB (NF-κB) in the dorsal root ganglia (DRG) is critical for development of neuropathic pain. The underlying mechanisms, however, are largely unknown. In the present work we tested if the activation of NF-κB is required for re-expression of Nav1.3, which is important for development of neuropathic pain, in uninjured DRG neurons. We found that intrathecal injection of pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, completely blocked the mechanical allodynia induced by L5 ventral root transection (L5-VRT), when applied 30 min before or 8h after operation, but at 7d after L5-VRT the same manipulation had no effect on established allodynia. Pre-treatment with PDTC also prevented the re-expression of Nav1.3 induced by L5-VRT. As our previous work has shown that up-regulation of tumor necrosis factor-alpha (TNF-α) in DRG is responsible for the re-expression of Nav1.3 in uninjured DRG neurons following L5 ventral root injury, we investigated whether activation of NF-κB is essential for the up-regulation of Nav1.3 by TNF-α. Results showed that application of rat recombinant TNF-α (rrTNF) into the cultured normal adult rat DRG neurons increased the immunoreactive (IR) of Nav1.3 localized mainly around the cell membrane and pre-treatment with PDTC blocked the change dose-dependently. The data suggested that injury to ventral root might lead to neuropathic pain and the re-expression of Nav1.3 in primary sensory neurons by activation of NF-κB.Copyright © 2010 Elsevier B.V. All rights reserved.

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