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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\u2003h to 7\u2003days 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\u2003G into normal sciatic nerve produced significant thermal hyperalgesia and mechanical allodynia of the ipsilateral hindpaw at 2\u20137\u2003days after injection. This was accompanied by increased deposition of C3 and recruitment of macrophages at 7\u2003days following injection. Complement inhibition using systemic injections of soluble complement receptor\u20031 (AVANT Immunotherapeutics, Inc., Needham, USA) into rats markedly suppressed C3 deposition and T\u2010cell 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.<\/jats:p>","DOI":"10.1111\/j.1460-9568.2007.05971.x","type":"journal-article","created":{"date-parts":[[2010,7,19]],"date-time":"2010-07-19T15:02:59Z","timestamp":1279551779000},"page":"3486-3500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Complement activation contributes to leukocyte recruitment and neuropathic pain following peripheral nerve injury in rats"],"prefix":"10.1111","volume":"26","author":[{"given":"Man","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip W.","family":"Peake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Charlesworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Tracey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gila","family":"Moalem\u2010Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,12,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.7.4708"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1113"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00331-6"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"6713","DOI":"10.1523\/JNEUROSCI.18-17-06713.1998","article-title":"Complement depletion reduces macrophage infiltration and activation during Wallerian degeneration and axonal regeneration","volume":"18","author":"Dailey A.T.","year":"1998","journal-title":"J. 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