Peri-sciatic administration of recombinant rat TNF-α induces mechanical allodynia via upregulation of TNF-α in dorsal root ganglia and in spinal dorsal horn: The role of NF-kappa B pathway
Peri-sciatic administration of recombinant rat TNF-α induces mechanical allodynia via upregulation of TNF-α in dorsal root ganglia and in spinal dorsal horn: The role of NF-kappa B pathway
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DOI：
10.1016/j.expneurol.2007.03.012
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发表时间：
2007-06
影响因子：
5.3
通讯作者：
Xu-Hong Wei;Y. Zang;Chang‐you Wu;Ji-Tian Xu;Wen-Jun Xin;Xian-Guo Liu
中科院分区：
文献类型：
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作者：
Xu-Hong Wei;Y. Zang;Chang‐you Wu;Ji-Tian Xu;Wen-Jun Xin;Xian-Guo Liu
以往的研究表明，神经损伤后，背根神经节（DRG）和脊髓背角中的肿瘤坏死因子-α（TNF-α）和TNF受体1（TNFR 1）上调，许多含TNF-α的神经元过表达TNFR 1。在本研究中，我们发现，大鼠坐骨周注射重组TNF-α（rrTNF），浓度分别为10、100和1000 pg/ml（每日一次，持续2天），可诱导双侧后爪的机械性异常性疼痛，持续约20天。注射rrTNF后第1天和第3天，同侧L4和L5背根节TNF-α和TNFR 1的免疫反应性（IR）显著增加，而对侧L5背根节TNF-α和TNFR 1的免疫反应性（IR）无明显变化。免疫荧光双标显示，在DRG中，TNF-α-IR的上调主要集中在神经元细胞，卫星胶质细胞的上调程度较低，而TNFR 1-IR的上调几乎局限于神经元细胞。TNF-α-IR在第3 ~ 14天双侧腰段脊髓背角也有增加，主要见于星形胶质细胞、小胶质细胞和神经元。此外，从rrTNF给药后第2天开始，在同侧L5 DRG和坐骨神经中观察到单核细胞/巨噬细胞和T淋巴细胞的进行性浸润。在每次注射rrTNF前30 min鞘内注射核因子-κ B（NF-κB）抑制剂PDTC（8.2 ng/10 μl）可完全阻断机械性痛觉超敏反应，并显著抑制TNF-α-IR和TNFR 1-IR的上调。结果表明，rrTNF的坐骨周给药可能通过自分泌机制通过激活NF-κB途径诱导机械性异常性疼痛。
Previous studies have shown that tumor necrosis factor-alpha (TNF-α) and TNF receptor 1 (TNFR1) in dorsal root ganglia (DRG) and in spinal dorsal horn are upregulated after nerve injury and that many TNF-α-containing neurons overexpress TNFR1. In the present study, we found that peri-sciatic administration of rat recombinant TNF-α (rrTNF) at the concentrations of 10, 100 and 1000 pg/ml (daily for 2 days) induced mechanical allodynia in bilateral hindpaws, lasting for about 20 days. The immunoreactivity (IR) of TNF-α and TNFR1 in the ipsilateral (but not in the contralateral) L4 and L5 DRGs increased significantly on day 1 and day 3 after administration of rrTNF, respectively. Double immunofluorescence staining revealed that in DRGs the increased TNF-α-IR was mainly in neuronal cells and with a lesser extent in satellite glial cells, while the upregulation of TNFR1-IR was almost restricted at neuronal cells. TNF-α-IR but not TNFR1-IR also increased in bilateral lumbar spinal dorsal horn from day 3 to day 14, which was observed in astrocytes, microglias and neurons. In addition, a progressive infiltration of monocyte/macrophages and T lymphocytes in the ipsilateral L5 DRG and sciatic nerve was observed, starting on day 2 following administration of rrTNF. Intrathecal delivery of PDTC (8.2 ng in 10 μl volume), a nuclear factor-kappa B (NF-κB) inhibitor, 30 min before each rrTNF administration blocked mechanical allodynia completely and inhibited the upregulation of TNF-α-IR and TNFR1-IR substantially. The results suggest that peri-sciatic administration of rrTNF may induce mechanical allodynia by an autocrine mechanism via activation of the NF-κB pathway.