Macrophage inflammatory protein-1α mediates the development of neuropathic pain following peripheral nerve injury through interleukin-1β up-regulation
Macrophage inflammatory protein-1α mediates the development of neuropathic pain following peripheral nerve injury through interleukin-1β up-regulation
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DOI：
10.1016/j.pain.2010.02.025
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发表时间：
2010-05-01
期刊：
影响因子：
7.4
通讯作者：
Kishioka, Shiroh
中科院分区：
文献类型：
--
作者：
Kiguchi, Norikazu;Maeda, Takehiko;Kishioka, Shiroh
在本研究中，我们研究了巨噬细胞炎性蛋白-1 α（MIP-1 α）在小鼠坐骨神经部分结扎（PSL）后神经病理性疼痛发病机制中的作用。PSL后MIP-1 α mRNA及其蛋白表达显著上调，定位于巨噬细胞和雪旺细胞。通过神经周围注射抗MIP-1 α（2 ng），可预防PSM诱导的持久触觉异常性疼痛和热痛觉过敏。神经内（20 ng）和神经周（100 ng）注射重组MIP-1 α引起假手术肢体的触觉异常性疼痛和热痛觉过敏。MIP-1 α受体（CCR 1和CCR 5）mRNA及其蛋白在PSL后SCN中表达上调，定位于巨噬细胞和雪旺细胞。通过神经周围注射（0.2nmol）针对CCR 1和CCR 5的siRNA来减弱PSL诱导的触觉异常性疼痛。另一方面，针对CCR 5的siRNA可以预防PSM诱导的热痛觉过敏，但不能预防CCR 1。巨噬细胞和雪旺细胞中的白细胞介素-1 β（IL-1 β）mRNA及其前体蛋白在PSL后的SCN中也上调，并且通过神经周围注射抗IL-1 β（2 ng）来预防PSL诱导的神经病理性疼痛。LPS诱导的IL-1 β上调被抗MIP-1 α和针对CCR 1和CCR 5的siRNA抑制。神经周围注射尼古丁（20 nmol），一种巨噬细胞抑制剂，可预防PSL诱导的神经性疼痛并抑制MIP-1 α和IL-1 β表达。总之，我们提出了一种源自巨噬细胞和许旺细胞的新型关键分子MIP-1 α，它似乎在PSL诱导的神经性疼痛的发展中发挥着至关重要的作用。(C)2010年国际疼痛研究协会。由Elsevier B出版。V.保留所有权利。
In the present study, we investigated the role of the macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of neuropathic pain following partial sciatic nerve ligation (PSL) in mice. MIP-1 alpha mRNA and its protein were dramatically up-regulated after PSL, and MIP-1 alpha was localized on macrophages and Schwann cells in the injured sciatic nerve (SCN). PSL-induced long-lasting tactile allodynia and thermal hyperalgesia were prevented by the perineural injection of anti-MIP-1 alpha (2 ng). Intraneural (20 ng) and perineural (100 ng) injection of recombinant MIP-1 alpha elicited tactile allodynia and thermal hyperalgesia in sham-operated limb. MIP-1 alpha receptors (CCR1 and CCR5) mRNA and their proteins were also up-regulated in the SCN after PSL, and were localized on macrophages and Schwann cells. PSL-induced tactile allodynia was attenuated by perineural injection (0.2 nmol) of siRNA against CCR1 and CCR5. On the other hand, PSL-induced thermal hyperalgesia was prevented by siRNA against CCR5, but not CCR1. Interleukin- 1 beta (IL-1 beta) mRNA and its precursor protein in macrophages and Schwann cells were also up-regulated in the SCN after PSL, and PSL-induced neuropathic pain was prevented by the perineural injection of anti-IL-1 beta (2 ng). PSL-induced IL-1 beta up-regulation was suppressed by anti-MIP-1 alpha and siRNA against CCR1 and CCR5. Perineural injection of nicotine (20 nmol), a macrophage suppressor, prevented PSL-induced neuropathic pain and suppressed MIP-1 alpha and IL-1 beta expressions. In conclusion, we propose a novel critical molecule MIP-1 alpha derived from macrophages and Schwann cells that appears to play a crucial role in the development of neuropathic pain induced by PSL. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.