Bilateral elevation of interleukin-6 protein and mRNA in both lumbar and cervical dorsal root ganglia following unilateral chronic compression injury of the sciatic nerve.

Bilateral elevation of interleukin-6 protein and mRNA in both lumbar and cervical dorsal root ganglia following unilateral chronic compression injury of the sciatic nerve.
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DOI:
10.1186/1742-2094-10-55
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发表时间:
2013-05-01
影响因子:
9.3
通讯作者:
Hradilová-Svíženská I
Hradilová-Svíženská I
中科院分区:
医学1区
文献类型:
--
作者:
Dubový P;Brázda V;Klusáková I;Hradilová-Svíženská I

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目前的研究表明,白细胞介素(IL)-6是神经系统对损伤反应的关键成分,具有多种作用。我们采用大鼠坐骨神经单侧慢性压迫性损伤(CCI)作为神经病理性疼痛的模型。采用免疫荧光、ELISA、Western blotting和原位杂交等方法检测CCI后双侧腰(L4-L5)和颈(C7-C8)背根节(DRG)IL-6蛋白和mRNA的变化。在1、3、7和14天后评估手术(CCI)和假手术(sham)大鼠。在同侧和对侧后爪和前爪中测量机械性痛觉过敏和热痛觉过敏的缩足阈值。所有CCI大鼠同侧后爪的机械痛敏阈值和热痛敏的退缩潜伏期均降低,而对侧前后爪的机械和热敏感性均无明显变化。在假手术大鼠两侧的后爪和前爪中未发现显著的行为变化,但在第3天双侧出现热超敏反应。单侧CCI的坐骨神经诱导双侧增加IL-6免疫染色的神经元体和卫星胶质细胞(SGC)周围的神经元的腰和颈DRG的神经元,与那些幼稚的对照组大鼠。通过ELISA和蛋白质印迹法证实了IL-6蛋白水平的这种双侧增加。CCI后大鼠两侧腰、颈背根节IL-6 mRNA表达增强。从假手术大鼠中取出的DRG显示出与在幼稚DRG中发现的类似的IL-6蛋白和mRNA染色模式,但在SGC中有更高的染色强度。IL-6蛋白和mRNA的双侧升高不仅限于与损伤神经同源的DRG,还扩展到与损伤神经异源的DRG。IL-6的结果表明,背根神经节对神经损伤的神经炎症反应沿着神经轴从腰段传播到远端颈段。这可能与颈DRG神经元对损伤的条件反射有关。
Current research implicates interleukin (IL)-6 as a key component of the nervous-system response to injury with various effects. We used unilateral chronic constriction injury (CCI) of rat sciatic nerve as a model for neuropathic pain. Immunofluorescence, ELISA, western blotting and in situ hybridization were used to investigate bilateral changes in IL-6 protein and mRNA in both lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) following CCI. The operated (CCI) and sham-operated (sham) rats were assessed after 1, 3, 7, and 14 days. Withdrawal thresholds for mechanical hyperalgesia and latencies for thermal hyperalgesia were measured in both ipsilateral and contralateral hind and fore paws. The ipsilateral hind paws of all CCI rats displayed a decreased threshold of mechanical hyperalgesia and withdrawal latency of thermal hyperalgesia, while the contralateral hind and fore paws of both sides exhibited no significant changes in mechanical or thermal sensitivity. No significant behavioral changes were found in the hind and fore paws on either side of the sham rats, except for thermal hypersensitivity, which was present bilaterally at 3 days. Unilateral CCI of the sciatic nerve induced a bilateral increase in IL-6 immunostaining in the neuronal bodies and satellite glial cells (SGC) surrounding neurons of both lumbar and cervical DRG, compared with those of naive control rats. This bilateral increase in IL-6 protein levels was confirmed by ELISA and western blotting. More intense staining for IL-6 mRNA was detected in lumbar and cervical DRG from both sides of rats following CCI. The DRG removed from sham rats displayed a similar pattern of staining for IL-6 protein and mRNA as found in naive DRG, but there was a higher staining intensity in SGC. Bilateral elevation of IL-6 protein and mRNA is not limited to DRG homonymous to the injured nerve, but also extended to DRG that are heteronymous to the injured nerve. The results for IL-6 suggest that the neuroinflammatory reaction of DRG to nerve injury is propagated alongside the neuroaxis from the lumbar to the remote cervical segments. This is probably related to conditioning of cervical DRG neurons to injury.
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发表时间: 1990-05-01
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