title: 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.
abstract: 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-α) 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 (10μM in 10μl volume) or A438079 (10μM in 10μl 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-α 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-α.
authors.affiliation: Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China.
authors.forename: Yan-Lu
authors.initials: YL
authors.lastname: Ying
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors.forename: Xu-Hong
authors.initials: XH
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen 518053, China. Electronic address: xuxuebing@hotmail.com.
authors.forename: Xue-Bing
authors.initials: XB
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China.
authors.forename: Shou-Zhang
authors.initials: SZ
authors.lastname: She
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors.forename: Xian-Guo
authors.initials: XG
authors.lastname: Liu
mesh_terms: D000818:Animals; D062109:Dermatologic Surgical Procedures / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D009132:Muscles / Q000601:surgery; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D010149:Postoperative Pain / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D058920:Purinergic P2X Receptor Antagonists / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D012867:Skin; D013116:Spinal Cord / Q000473:pathology*; D013777:Tetrazoles / Q000627:therapeutic use; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C523668:3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methylpyridine; D005904:Glial Fibrillary Acidic Protein; D058920:Purinergic P2X Receptor Antagonists; D011725:Pyridines; D058486:Receptors, Purinergic P2X7; D013777:Tetrazoles
keywords: Chronic postsurgical pain; Microglia; P2X7 receptor; Tumor necrosis factor-alpha