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)
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)
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背根神经节卫星胶质细胞中 P2X7R/ERK 信号传导在皮肤/肌肉切开和牵拉 (SMIR) 引起的慢性术后疼痛发展中的作用
DOI：
10.1016/j.bbi.2017.11.011
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发表时间：
2018-03-01
影响因子：
15.1
通讯作者：
Ruan, Xiangcai
中科院分区：
文献类型：
--
作者：
Song, Jingnian;Ying, Yanlu;Ruan, Xiangcai
慢性术后疼痛的机制仍有待阐明。采用大鼠皮肤/肌肉切开牵拉（SMIR）术后疼痛模型，观察了大鼠腰3背根神经节（L3 DRG）细胞外调节蛋白激酶（ERK）信号通路c-Raf、MEK（ERK激酶）和ERK 1/2的磷酸化。鞘内注射ERK特异性抑制剂SCH 772984可抑制SMIR诱导的机械性痛觉超敏反应。此外，SMIR上调L3 DRG中的肿瘤坏死因子α（TNF α），这可以被SCH 772984抑制。鞘内注射TNF拮抗剂Etanercept也能抑制SMIR诱导的机械性痛觉超敏反应和L3 DRG ERK磷酸化的增加。此外，免疫荧光数据显示，P2 X7 R只位于GFAP标记的卫星胶质细胞，并高度共定位与p-ERK 1/2后SMIR。P2 X7受体拮抗剂Brilliant Blue G（BBG）预处理可阻断机械性痛觉超敏反应，抑制c-Raf、MEK、ERK 1/2的磷酸化，降低TNF-α的表达。最后，鞘内注射BzATP产生机械性异常性疼痛，并诱导L3 DRG卫星胶质细胞ERK磷酸化。因此，在L3 DRG中的卫星神经胶质细胞中的P2 X7 R活化，导致ERK通路活化和TNF-α产生之间的正反馈，被认为参与SMIR后慢性手术后疼痛的诱导。(C)2017爱思唯尔公司All rights reserved.
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 (TNF alpha) 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-alpha. 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-alpha production, is suggested to be involved in the induction of chronic postsurgical pain following SMIR. (C) 2017 Elsevier Inc. All rights reserved.