The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection

The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection
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DRG 和脊髓背角 IL-6 的上调导致 L5 腹根横断后的神经性疼痛

DOI:
10.1016/j.expneurol.2012.12.007
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发表时间:
2013-03
影响因子:
5.3
通讯作者:
Liu, Xian-Guo
Liu, Xian-Guo
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Feng-Ying;Li, Yong-Yong;Zang, Ying;Liu, Xian-Guo

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我们的前期工作表明,促炎细胞因子肿瘤坏死因子-α(TNF-α)在L5-VRT引起的神经病理性疼痛中起重要作用。在目前的工作中,我们评估的作用,白细胞介素-6(IL-6),另一个关键的炎症细胞因子,在L5-VRT模型。我们发现,IL-6在同侧L4和L5背根神经节(DRG)神经元和双侧腰髓后L5-VRT上调。双重免疫荧光染色显示,在DRG中,IL-6的免疫反应性(IR)增加几乎局限于神经元细胞,而在脊髓背角中,IL-6-IR在胶质细胞(星形胶质细胞和小胶质细胞)和神经元中均上调。鞘内注射IL-6中和抗体显著延迟了L5-VRT后双侧后爪机械性异常性疼痛的诱导。此外,通过腹膜内沙利度胺抑制TNF-α合成可防止L5-VRT后机械性异常性疼痛和DRG中IL-6的上调。提示运动纤维损伤后传入神经元和脊髓中IL-6的表达增加与神经病理性疼痛的发生有关,TNF-α参与了IL-6的上调。
Our previous works have shown that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in neuropathic pain produced by lumber 5 ventral root transection (L5-VRT). In the present work we evaluate the role of interleukin-6 (IL-6), another key inflammatory cytokine, in the L5-VRT model. We found that IL-6 was up-regulated in the ipsilateral L4 and L5 dorsal root ganglian (DRG) neurons and in bilateral lumbar spinal cord following L5-VRT. Double immunofluorescence stainings revealed that in DRGs the increased immunoreactivity (IR) of IL-6 was almost restricted in neuronal cells, while in the spinal dorsal horn IL-6-IR up-regulated in both glial cells (astrocyte and microglia) and neurons. Intrathecal administration of IL-6 neutralizing antibody significantly delayed the induction of mechanical allodynia in bilateral hindpaws after L5-VRT. Furthermore, inhibition of TNF-α synthesis by intraperitoneal thalidomide prevented both mechanical allodynia and the up-regulation of IL-6 in DRGs following L5-VRT. These data suggested that the increased IL-6 in afferent neurons and spinal cord contribute to the development of neuropathic pain following motor fiber injury, and that TNF-α is responsible for the up-regulation of IL-6.
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