Complement activation contributes to leukocyte recruitment and neuropathic pain following peripheral nerve injury in rats
Complement activation contributes to leukocyte recruitment and neuropathic pain following peripheral nerve injury in rats
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DOI：
10.1111/j.1460-9568.2007.05971.x
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发表时间：
2007-12-01
影响因子：
3.4
通讯作者：
Moalem-Taylor, Gila
中科院分区：
文献类型：
--
作者：
Li, Man;Peake, Philip W.;Moalem-Taylor, Gila
补体激活会引发炎症，并与疼痛相关的神经系统疾病有关。然而，补体在神经病理性疼痛中的作用还没有明确的定义。在这项研究中，我们测试了部分结扎大鼠坐骨神经(一种广泛使用的神经病理性疼痛模型)是否激活补体，以及周围神经中补体的激活或抑制是否影响白细胞募集和神经病理性疼痛。我们发现C3在损伤神经中的沉积从6h到7d显著增加，并与热痛觉过敏和机械性痛觉过敏的程度有关。然而，没有检测到膜攻击复合体的沉积。向正常坐骨神经内注射聚集的大鼠免疫球蛋白G激活补体，在注射后2~7天，可引起同侧后爪的热痛敏和机械性超敏。这伴随着C3沉积的增加和巨噬细胞在注射后7天的募集。大鼠全身注射可溶性补体受体1(美国Needham公司的Avant免疫疗法公司)抑制补体，显著抑制C3沉积和T细胞和巨噬细胞向受损神经的募集，并显著缓解热痛觉过敏和机械性痛觉过敏。这些结果表明，神经中C3的激活有助于周围神经损伤后炎性细胞的增加和神经病理性疼痛行为。补体抑制可能是神经病理性疼痛的一种潜在的治疗方法。
Complement activation triggers inflammation and has been implicated in neurological diseases associated with pain. However, the role of complement in neuropathic pain has not been clearly defined. In this study, we tested whether complement is activated by partial ligation of the rat sciatic nerve, a widely used model of neuropathic pain, and whether complement activation or inhibition in peripheral nerve influences leukocyte recruitment and neuropathic pain. We found that C3 deposition significantly increased from 6 h to 7 days in the injured nerve and was associated with the extent of thermal hyperalgesia and mechanical allodynia. However, no deposition of the membrane attack complex was detected. Complement activation by endoneurial injection of aggregated rat immunoglobulin G into normal sciatic nerve produced significant thermal hyperalgesia and mechanical allodynia of the ipsilateral hindpaw at 2-7 days after injection. This was accompanied by increased deposition of C3 and recruitment of macrophages at 7 days following injection. Complement inhibition using systemic injections of soluble complement receptor 1 (AVANT Immunotherapeutics, Inc., Needham, USA) into rats markedly suppressed C3 deposition and T-cell and macrophage recruitment to the injured nerve, and produced significant alleviation of thermal hyperalgesia and mechanical allodynia. These results demonstrate that C3 activation in the nerve contributes to increased infiltration of inflammatory cells and to neuropathic pain behaviors following peripheral nerve injury. Complement inhibition may be a potential therapeutic treatment for neuropathic pain.