PMID- 25242211 OWN - NLM STAT- MEDLINE DCOM- 20141217 LR - 20220311 IS - 1090-2430 (Electronic) IS - 0014-4886 (Linking) VI - 261 DP - 2014 Nov TI - Over-expression of P2X7 receptors in spinal glial cells contributes to the development of chronic postsurgical pain induced by skin/muscle incision and retraction (SMIR) in rats. PG - 836-43 LID - S0014-4886(14)00290-8 [pii] LID - 10.1016/j.expneurol.2014.09.007 [doi] AB - Many patients suffer from chronic postsurgical pain (CPSP) following surgery, and the underlying mechanisms are poorly understood. In the present work, with use of the skin/muscle incision and retraction (SMIR) model, the role of P2X7 receptors (P2X7Rs) in spinal glial cells in the development of CPSP was evaluated. Consistent with previous reports, we found that SMIR decreased the ipsilateral 50% paw withdrawal threshold (PWT), lasting for at least 2weeks. No injury was done to L3 dorsal root ganglia (DRG) neurons and no axonal or Schwann cell damage at the retraction site in the saphenous nerve was observed 7days after SMIR. The results of immunofluorescence showed that both microglia and astrocytes were activated in the spinal dorsal horn following SMIR. In addition, both P2X7Rs and tumor necrosis factor-alpha (TNF-alpha) were up-regulated following SMIR. Double immunofluorescence staining revealed that the up-regulated P2X7R immunoreactivity was mainly located in microglia, and to a lesser extent in astrocytes, but not in neurons. Intrathecal delivery of specific P2X7R antagonist BBG (10muM in 10mul volume) or A438079 (10muM in 10mul volume), started 30min before the surgery and once daily thereafter for 7days, prevented the mechanical allodynia. Intrathecal injection of BBG inhibited the activation of microglia and astrocytes, and the up-regulation of TNF-alpha induced by SMIR. These data suggest that P2X7Rs in the spinal dorsal horn might mediate the development of CPSP via activation of glial cells and up-regulation of TNF-alpha. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Ying, Yan-Lu AU - Ying YL AD - Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China. FAU - Wei, Xu-Hong AU - Wei XH AD - Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China. FAU - Xu, Xue-Bing AU - Xu XB AD - Department of Anesthesiology, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen 518053, China. Electronic address: xuxuebing@hotmail.com. FAU - She, Shou-Zhang AU - She SZ AD - Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China. FAU - Zhou, Li-Jun AU - Zhou LJ AD - Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China. FAU - Lv, Jing AU - Lv J AD - Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China. FAU - Li, Dai AU - Li D AD - Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China. FAU - Zheng, Bin AU - Zheng B AD - Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China. FAU - Liu, Xian-Guo AU - Liu XG AD - Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140919 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Purinergic P2X Receptor Antagonists) RN - 0 (Pyridines) RN - 0 (Receptors, Purinergic P2X7) RN - 0 (Tetrazoles) SB - IM MH - Animals MH - Dermatologic Surgical Procedures/adverse effects MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Functional Laterality MH - Glial Fibrillary Acidic Protein/metabolism MH - Male MH - Microscopy, Electron, Transmission MH - Muscles/surgery MH - Neuroglia/*metabolism/ultrastructure MH - Pain, Postoperative/drug therapy/etiology/*pathology MH - Purinergic P2X Receptor Antagonists/therapeutic use MH - Pyridines/therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Purinergic P2X7/*metabolism MH - Skin MH - Spinal Cord/*pathology MH - Tetrazoles/therapeutic use MH - Time Factors MH - Up-Regulation/drug effects/physiology OTO - NOTNLM OT - Chronic postsurgical pain OT - Microglia OT - P2X7 receptor OT - Tumor necrosis factor-alpha EDAT- 2014/09/23 06:00 MHDA- 2014/12/18 06:00 CRDT- 2014/09/23 06:00 PHST- 2014/04/26 00:00 [received] PHST- 2014/08/10 00:00 [revised] PHST- 2014/09/05 00:00 [accepted] PHST- 2014/09/23 06:00 [entrez] PHST- 2014/09/23 06:00 [pubmed] PHST- 2014/12/18 06:00 [medline] AID - S0014-4886(14)00290-8 [pii] AID - 10.1016/j.expneurol.2014.09.007 [doi] PST - ppublish SO - Exp Neurol. 2014 Nov;261:836-43. doi: 10.1016/j.expneurol.2014.09.007. Epub 2014 Sep 19.