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
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
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脊髓胶质细胞中 P2X7 受体的过度表达导致大鼠皮肤/肌肉切开和牵拉 (SMIR) 诱导的慢性术后疼痛的发生
DOI：
10.1016/j.expneurol.2014.09.007
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发表时间：
2014-11-01
影响因子：
5.3
通讯作者：
Liu, Xian-Guo
中科院分区：
文献类型：
--
作者：
Ying, Yan-Lu;Wei, Xu-Hong;Liu, Xian-Guo
许多患者在手术后遭受慢性术后疼痛（CPSP），并且对其潜在机制知之甚少。在本工作中，使用皮肤/肌肉切开和牵拉（SMIR）模型，脊髓胶质细胞中的P2 X7受体（P2 X7 Rs）在CPSP的发展中的作用进行了评估。与以前的报道一致，我们发现SMIR降低同侧50%缩爪阈值（PWT），持续至少2周。SMIR后7 d，L3背根神经节（DRG）神经元无明显损伤，隐神经牵开处无轴突或雪旺细胞损伤。免疫荧光结果显示，SMIR后脊髓背角小胶质细胞和星形胶质细胞均被激活。此外，SMIR后P2 X7 Rs和肿瘤坏死因子-α（TNF-α）均上调。免疫荧光双标显示P2 X7 R免疫反应阳性表达主要位于小胶质细胞，其次为星形胶质细胞，而神经元中无P2 X7 R表达。在手术前30分钟开始鞘内递送特异性P2 X7 R拮抗剂BBG（10 μ M，10 μ l体积）或A438079（10 μ M，10 μ l体积），此后每天一次，持续7天，预防机械性异常性疼痛。鞘内注射BBG可抑制SMIR诱导的小胶质细胞和星形胶质细胞的活化及TNF-α的上调。这些数据表明，P2 X7 Rs在脊髓背角可能介导的发展，通过激活胶质细胞和上调TNF-α的CPSP。(C)2014爱思唯尔公司All rights reserved.
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 2 weeks. 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 7 days 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 immunofiuorescence 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 (10 mu M in 10 mu l volume) or A438079 (10 mu M in 10 mu l volume), started 30 min before the surgery and once daily thereafter for 7 days, 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. (C) 2014 Elsevier Inc. All rights reserved.