Involvement of RVM-expressed P2X7 receptor in bone cancer pain: Mechanism of descending facilitation
Involvement of RVM-expressed P2X7 receptor in bone cancer pain: Mechanism of descending facilitation
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DOI：
10.1016/j.pain.2014.01.011
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发表时间：
2014-04-01
期刊：
影响因子：
7.4
通讯作者：
Zhao, Zhi Qi
中科院分区：
文献类型：
--
作者：
Huang, Zhang Xiang;Lu, Zhi Jie;Zhao, Zhi Qi
骨癌患者通常会经历严重、难以忍受且难以控制的骨痛。延髓头端腹内侧（RVM）通过降低脊髓伤害感受而在慢性疼痛的发展中发挥重要作用。令人信服的证据表明，神经胶质 P2X7 受体 (P2X7R) 参与慢性疼痛综合征的诱导和维持。本研究探讨了诱导骨癌痛的胶质细胞激活和 P2X7R 表达的机制。结果表明，骨癌大鼠RVM中的小胶质细胞和星形胶质细胞显着激活，P2X7R的表达显着上调。将 P2X7R 抑制剂亮蓝 G (BBG) 注射到 RVM 中可显着减轻癌症大鼠的疼痛行为，RVM 内注射针对 RVM 中 P2X7R 的 RNA 干扰也支持这一效果。研究表明，RVM 中小胶质细胞表达的 P2X7R 的激活有助于骨癌疼痛。鉴于 RVM 中的 5-HT 参与调节脊髓伤害感受，因此在脊髓中解决了 5-HT 和 Fos 表达的变化。 BBG 或 RVM 中靶向 P2X7 的小干扰 RNA 对 P2X7R 的抑制显着降低了脊髓中的 5-HT 水平和 Fos 表达。数据清楚地表明，RVM 中小胶质细胞 P2X7R 的激活通过下行疼痛促进系统上调脊髓 5HT 水平，从而促进骨癌疼痛的发生。皇冠版权所有 (C) 2014 由 Elsevier B.V. 代表国际疼痛研究协会出版。版权所有。
Patients with bone cancer commonly experience bone pain that is severe, intolerable, and difficult to manage. The rostral ventromedial medulla (RVM) plays an important role in the development of chronic pain via descending facilitation of spinal nociception. The compelling evidence shows that glial P2X7 receptor (P2X7R) is involved in the induction and maintenance of chronic pain syndromes. The present study explored the mechanism of glial activation and P2X7R expression underlying the induction of bone cancer pain. The results demonstrated that microglia and astrocytes in the RVM were markedly activated in bone cancer rats, and the expression of P2X7R was significantly upregulated. Injection of Brilliant Blue G (BBG), an inhibitor of P2X7R, into the RVM significantly alleviated pain behaviors of cancer rats, which was supported by intra-RVM injection of RNA interference targeting the P2X7R in the RVM. It is suggested that activation of microglia-expressed P2X7R in the RVM contributes to bone cancer pain. Given that 5-HT in the RVM is involved in modulating spinal nociception, changes in 5-HT and Fos expression were addressed in the spinal cord. Inhibition of P2X7R by BBG or small-interference RNA targeting P2X7 in the RVM markedly reduced 5-HT level and Fos expression in the spinal cord. The data clearly suggest that the activation of microglial P2X7R in the RVM contributes to the development of bone cancer pain via upregulation of spinal 5HT levels by the descending pain facilitatory system. Crown Copyright (C) 2014 Published by Elsevier B.V. on behalf of International Association for the Study of Pain. All rights reserved.