Inhibition of NF-kappaB prevents mechanical allodynia induced by spinal ventral root transection and suppresses the re-expression of Nav1.3 in DRG neurons in vivo and in vitro
Inhibition of NF-kappaB prevents mechanical allodynia induced by spinal ventral root transection and suppresses the re-expression of Nav1.3 in DRG neurons in vivo and in vitro
复制标题
体内和体外抑制 NF-kappaB 可预防脊髓腹根横断引起的机械性异常性疼痛，并抑制 DRG 神经元中 Nav1.3 的重新表达
DOI：
10.1016/j.brainres.2010.09.048
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发表时间：
2010-12-06
期刊：
影响因子：
2.9
通讯作者：
Liu, Xian-Guo
中科院分区：
文献类型：
--
作者：
Zang, Ying;He, Xin-Hua;Liu, Xian-Guo
背根神经节 (DRG) 中核因子 kappaB (NF kappa B) 的激活对于神经性疼痛的发生至关重要。然而，其潜在机制在很大程度上尚不清楚。在目前的工作中，我们测试了 Nav1 3 的重新表达是否需要激活 NF kappa B，这对于未受伤的 DRG 神经元中神经性疼痛的发生非常重要。我们发现鞘内注射吡咯烷二硫代氨基甲酸酯 (PDTC) NF kappa B 抑制剂，在术前 30 ram 或术后 8 小时应用时，完全阻断了由 L5 腹侧根横断（L5 VRT）引起的机械异常性疼痛，但在 L5 VRT 后 7 d，相同的操作对已建立的异常性疼痛没有影响。PDTC 预处理也阻止了 L5 VRT 诱导的 Nav1 3 的再表达。正如我们之前的工作表明，DRG 中肿瘤坏死因子 α（TNF-α）的上调是由于 L5 腹侧根损伤后未损伤的 DRG 神经元中 Nav1 3 的重新表达，我们研究了 NF kappa B 的激活是否对于 TNF α 上调 Nav1 3 至关重要。结果表明，将大鼠重组 TNF α (nTNF) 应用于培养的正常成年大鼠 DRG 神经元中，增加了主要位于细胞膜周围的 Nav1 3 的免疫反应性 (IR)，并且用 PDTC 预处理可剂量依赖性地阻断这种变化。腹根可能会导致神经性疼痛，并且通过激活 NF-kappa B (C) 2010 Elsevier B V 保留原代感觉神经元中 Nav1 3 的重新表达
Activation of nucleus factor kappaB (NF kappa B) 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 kappa B 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 kappa B inhibitor, completely blocked the mechanical allodynia induced by L5 ventral root transection (L5 VRT), when applied 30 ram before or 8 h after operation, but at 7 d 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-alpha) 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 kappa B is essential for the up regulation of Nav1 3 by TNF alpha Results showed that application of rat recombinant TNF alpha (nTNF) 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-kappa B (C) 2010 Elsevier B V All rights reserved