Li Man, Peake Philip W, Charlesworth John A, Tracey David J, Moalem-Taylor Gila
School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Eur J Neurosci. 2007 Dec;26(12):3486-500. doi: 10.1111/j.1460-9568.2007.05971.x. Epub 2007 Dec 4.
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.
补体激活引发炎症，并与伴有疼痛的神经疾病有关。然而，补体在神经性疼痛中的作用尚未明确界定。在本研究中，我们测试了补体是否由大鼠坐骨神经部分结扎激活（一种广泛使用的神经性疼痛模型），以及外周神经中的补体激活或抑制是否会影响白细胞募集和神经性疼痛。我们发现，在受损神经中，C3沉积从6小时到7天显著增加，并与热痛觉过敏和机械性异常性疼痛的程度相关。然而，未检测到膜攻击复合物的沉积。通过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天产生同侧后爪明显的热痛觉过敏和机械性异常性疼痛。这伴随着注射后7天C3沉积增加和巨噬细胞募集。使用全身注射可溶性补体受体1（美国尼德姆市AVANT免疫治疗公司）对大鼠进行补体抑制，显著抑制了C3沉积以及T细胞和巨噬细胞向受损神经的募集，并显著减轻了热痛觉过敏和机械性异常性疼痛。这些结果表明，神经中的C3激活导致炎症细胞浸润增加以及外周神经损伤后的神经性疼痛行为。补体抑制可能是神经性疼痛的一种潜在治疗方法。
