Interleukin-17 Contributes to Neuroinflammation and Neuropathic Pain Following Peripheral Nerve Injury in Mice
Interleukin-17 Contributes to Neuroinflammation and Neuropathic Pain Following Peripheral Nerve Injury in Mice
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DOI：
10.1016/j.jpain.2010.08.003
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发表时间：
2011-03-01
期刊：
影响因子：
4
通讯作者：
Moalem-Taylor, Gila
中科院分区：
文献类型：
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作者：
Kim, Cristina Fabiola;Moalem-Taylor, Gila
细胞因子是炎症和免疫反应的重要介质，在周围神经损伤后神经病理性疼痛的病理生理过程中起着重要作用。最近，一种新的促炎细胞因子，白细胞介素（IL）-17，被发现在神经系统的广泛的炎症和自身免疫性疾病中协调炎症反应。在这里，我们研究了IL-17在介导神经炎症和疼痛超敏性的神经病理性疼痛模型的部分结扎小鼠坐骨神经的作用。与野生型相比，IL-17敲除（KO）小鼠显示出显著降低的机械性疼痛超敏性以及T细胞和巨噬细胞向受损坐骨神经和L3-L5背根神经节的浸润减少，以及脊髓L3-5背角和腹角中小胶质细胞和星形胶质细胞的活化减少。此外，足底和神经内注射重组IL-17到后爪和坐骨神经，分别诱导机械异常性疼痛和热痛觉过敏，而鞘内注射产生热痛觉过敏。IL-17给药与注射后爪中浸润中性粒细胞和活化树突状细胞以及注射坐骨神经中浸润中性粒细胞数量的显著增加相关。两者合计，我们的研究结果表明，IL-17有助于调节免疫细胞浸润和神经胶质细胞活化后周围神经损伤和随后的neuropathic pain.Perspective：IL-17是一个重要的调节免疫反应，并参与诱导和介导促炎反应。使用IL-17 KO小鼠，我们已经证明IL-17有助于神经病理性损伤后的神经炎症反应和疼痛超敏反应。这项工作确定了IL-17作为神经性疼痛的潜在治疗靶点。(C)2011年美国疼痛协会American Pain Society
Cytokines, essential mediators of inflammatory and immune responses, play an important role in the pathophysiological processes associated with neuropathic pain following peripheral nerve injury. Recently, a novel proinflammatory cytokine, the interleukin (IL)-17, was found to orchestrate inflammatory responses in a wide range of inflammatory and autoimmune diseases of the nervous system. Here, we investigated the role of IL-17 in mediating neuroinflammation and pain hypersensitivity using the neuropathic pain model of partial ligation of the sciatic nerve in mice. Compared to wild-type, IL-17 knockout (KO) mice displayed significantly decreased mechanical pain hypersensitivity as well as decreased infiltration of T cells and macrophages to the injured sciatic nerves and the L3-L5 dorsal root ganglia and decreased activation of microglia and astrocytes in the L3-5 dorsal and ventral horns of the spinal cord. Further, intraplantar and intraneural injection of recombinant IL-17 into the hind paw and the sciatic nerve, respectively, induced both mechanical allodynia and thermal hyperalgesia, whereas intrathecal injection produced thermal hyperalgesia. IL-17 administration was associated with a significant increase in the numbers of infiltrating neutrophils and activated dendritic cells in the injected hind paws and infiltrating neutrophils in the injected sciatic nerves. Taken together, our results demonstrate that IL-17 contributes to the regulation of immune cell infiltration and glial activation after peripheral nerve injury and the ensuing neuropathic pain.Perspective: IL-17 is an important regulator of immune responses and is involved in inducing and mediating proinflammatory reactions. Using IL-17 KO mice, we have demonstrated that IL-17 contributes to neuroinflammatory responses and pain hypersensitivity following neuropathic injury. This work identifies IL-17 as a potential therapeutic target in neuropathic pain. (C) 2011 by the American Pain Society