激活α2A肾上腺素受体抑制背根神经节卫星胶质细胞激活缓解镜像痛敏

Activation of α2A adrenergic receptor alleviates mirror-image pain via inhibiting the activation of dorsal root ganglia satellite glia

摘要:

目的：一侧损伤常引发对侧疼痛反应，称为镜像痛敏 (mirror-image pain, MIP)，给病人带来严重的身心负担。目前关于MIP的病理机制众说纷纭，无明确靶标，限制了疼痛治疗。本研究拟阐释背根神经节 (dorsal root ganglion, DRG) 中α2A肾上腺素受体α(2A)AR和神经胶质细胞介导MIP的发生机制。方法：采用行为药理学、实时荧光定量PCR、免疫荧光和免疫印记等实验技术。结果：DRG中 α(2A)AR参与MIP的发生发展，而激活α(2A)AR显著缓解了MIP行为。疼痛刺激下，双侧DRG中胶质细胞差异表达，而激活α(2A)AR显著激活了DRG中的胶质细胞。此外，激活α(2A)AR显著降低卫星胶质细胞中α(2A)AR的表达，而不影响小胶质细胞中α(2A)AR的表达。结论：DRG卫星胶质细胞中的α(2A)AR是MIP的重要分子传感器，激活α(2A)AR改善MIP行为。。

Abstract:

Objective: Unilateral injury often causes contralateral pain response, which is called mirror-image pain (MIP), and brings serious physical and mental burden to patients. At present, the pathological mechanism of MIP is controversial, and there is no clear target, which limits the treatment of pain. The aim of this study was to elucidate the mechanism of α(2A)AR and glial cell-mediated MIP in dorsal root ganglion (DRG). Methods: Behavioral pharmacology, real-time fluorescence quantitative PCR, immunofluorescence and immunoblotting were used. Results: α(2A)AR was involved in the development of MIP in DRG, and activation of α(2A)AR significantly attenuated MIP. Under pain stimulation, glial cells in bilateral DRG were differentially expressed, and activation of α(2A)AR significantly activated glial cells in DRG. Furthermore, activation of a (2A)AR significantly reduced a (2A)AR expression in satellite glia, but not in microglia. Conclusion: α(2A)AR in DRG satellite glia is an important molecular sensor of MIP, and activation of α(2A)AR improves the MIP related behavior.