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Brain Behav Immun:The role of P2X7R/ERK signaling in dorsal root ganglia satellite glial cells in the development of chronic postsurgical pain induced by skin/muscle incision and retraction (SMIR).

2018-08-30 10:17  来源:未知  编辑:高国雷   点击:
 
Song J1Ying Y2Wang W3Liu X4Xu X5Wei X6Ruan X7.

Author information

1
Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China; Department of Anesthesiology, Hainan General Hospital, Xiuhua Rd., Haikou, Hainan 570311, China.
2
Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China.
3
Department of Physiology and Pain Research Center, Zhongshan School of Medicine Sun Yat-sen University, Guangzhou 510080, China.
4
Department of Physiology and Pain Research Center, Zhongshan School of Medicine Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong, China.
5
Department of Anesthesiology, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen 518053, China. Electronic address: xuxb@hku-szh.org.
6
Department of Physiology and Pain Research Center, Zhongshan School of Medicine Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou, Guangdong, China. Electronic address: weixhong@mail.sysu.edu.cn.
7
Department of Anesthesiology, Guangzhou First People's Hospital, Guangzhou Medical University, 602 Renminbei Rd., Guangzhou 510180, China. Electronic address: xc_ruan@gzhmu.edu.cn.

Abstract

The mechanisms of chronic postsurgical pain remain to be elucidated. We reported here that skin/muscle incision and retraction (SMIR), a rat model of postsurgical pain, phosphorylated the extracellular regulated protein kinases (ERK) signaling components c-Raf, MEK (ERK kinase) and ERK1/2 in lumbar 3 dorsal root ganglion (L3 DRG) in rats. Intrathecal injection of ERK specific inhibitor SCH772984 suppressed the mechanical allodynia induced by SMIR. Furthermore, SMIR upregulated tumor necrosis factor alpha (TNFα) in L3 DRG, which could be inhibited by SCH772984. Intrathecal injection of TNF antagonist Etanercept could also inhibit the mechanical allodynia and the increased ERK phosphorylation in L3 DRG induced by SMIR. In addition, immunofluorescent data showed that P2X7R was located exclusively in GFAP labeled satellite glial cells and was highly colocalized with p-ERK1/2 following SMIR. Pretreatment with P2X7R antagonist Brilliant Blue G (BBG) could also block the mechanical allodynia, inhibited the phosphorylation of c-Raf, MEK, ERK1/2, and decrease the expression of TNF-α. Finally, intrathecal injection of BzATP produced mechanical allodynia and induced ERK phosphorylation in satellite glial cells in L3 DRG. Thus, P2X7R activation in satellite glial cells in L3 DRG, leading to a positive feedback between ERK pathway activation and TNF-α production, is suggested to be involved in the induction of chronic postsurgical pain following SMIR.

KEYWORDS:

Chronic postsurgical pain; Dorsal root ganglia; Extracellular signal-regulated kinase; P2X7 receptor; Tumor necrosis factor alpha


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