The complement component C5a receptor mediates pain and inflammation in a postsurgical pain model

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• 作者：De-Yong Liang^a ; ^b ; ^{dyliang@stanford.edu} ; XiangQi Li^b ; Xiaoyu Shi^b ; Yuan Sun^a ; ^b ; Peyman Sahbaie^a ; ^b ; Wen-Wu Li^a ; ^b ; J. David Clark^a ; ^b
• 关键词：Incision ; Complement ; C5a receptor ; Pain ; Inflammation ; Nerve growth factor ; IL-1¦Â ; Mouse
• 刊名：Pain
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：153
• 期：2
• 页码：366-372
• 全文大小：604 K

文摘

The complement system is an important part of innate immunity. Complement activation generates a set of effector molecules with diverse biological functions. C5a is a crucial terminal component of the complement cascade. Several reports suggest that C5a can support nociceptive sensitization and inflammation in various models, including models of incisional pain. However, information concerning the differential effects of C5a on specific modalities of nociception, the role of C5a in supporting neutrophil infiltration, secondary nociceptive mediator generation, and the location of the relevant populations of C5a receptors supporting incisional sensitization are needed. In these studies we utilized C5a receptor-null mice (C5aR^{??/sup>) and matched controls to study nociceptive changes after hind paw incision. Heat hyperalgesia and mechanical allodynia were measured for 4 days after incision. We also followed hind paw edema, wound area neutrophil infiltration using the myeloperoxidase assay, and interleukin-1¦Â and nerve growth factor levels using both enzyme-linked immunosorbent assay and immunohistochemical techniques. The main findings were: (1) Heat vs mechanical nociceptive sensitization after incision were differentially reduced in C5aR??/sup> mice, with thermal sensitization affected throughout the postincisional period but mechanical sensitization affected only at later time points; (2) Edema developed after incision in wild-type mice but only slightly and transiently in C5aR??/sup> mice, and (3) Deletion of C5aR blocked interleukin-1¦Â and nerve growth factor production near the wound site. These findings demonstrate that the complement system component C5a is a novel biomarker and mediator associated with postsurgical nociceptive processing. C5aR may provide a novel target for the control of pain and inflammation after surgery.}