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电针对背根神经节神经元中 AXL 表达的抑制作用及其对神经结扎诱导的神经病理性疼痛大鼠中 AXL 抑制剂镇痛效果的增强作用。

Electro-acupuncture Suppresses AXL Expression in Dorsal Root Ganglion Neurons and Enhances Analgesic Effect of AXL Inhibitor in Spinal Nerve Ligation Induced-Neuropathic Pain Rats.

机构信息

Institute of Neuroscience, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.

出版信息

Neurochem Res. 2021 Mar;46(3):504-512. doi: 10.1007/s11064-020-03185-x. Epub 2021 Jan 2.

Abstract

Electro-acupuncture (EA) has been used for clinic analgesia for many years. However, its mechanisms are not fully understood. We recently reported that AXL, a tyrosine kinase receptor, contributes to the peripheral mechanism of neuropathic pain. We here aim to figure out the significance of EA on neuropathic pain mediated by AXL in dorsal root ganglion (DRG). Spinal nerve ligation (SNL) was used as a neuropathic pain model. EA was applied at ''Huantiao'' (GB-30) and ''Yanglingquan'' (GB-34) acupoints for 30 min daily from day 7 to day 10 after SNL. EA not only gradually attenuated SNL-induced mechanical allodynia, but also suppressed the expression of phosphorylated AXL (p-AXL) and AXL in injured DRGs of SNL rats examined by western blotting and immunofluorescence. Moreover, intrathecal injection of the subthreshold dose of AXL inhibitor TP0903, significantly prolonged the analgesic time of single EA treatment and enhanced the analgesic effect of repeated EA treatments, suggesting a synergic effect of EA and AXL inhibitor. These results indicate that AXL signaling underlies EA analgesia and combination of AXL inhibitor and EA might be a new strategy for clinic analgesia on neuropathic pain.

摘要

电针(EA)已在临床上用于镇痛多年。然而,其机制尚不完全清楚。我们最近报道,酪氨酸激酶受体 AXL 有助于神经性疼痛的外周机制。我们旨在探讨 EA 对 DRG 中 AXL 介导的神经性疼痛的意义。脊神经结扎(SNL)被用作神经性疼痛模型。从 SNL 后第 7 天到第 10 天,每天在“环跳”(GB-30)和“阳陵泉”(GB-34)穴位进行 30 分钟的 EA。EA 不仅逐渐减轻 SNL 引起的机械性痛觉过敏,而且通过 Western blot 和免疫荧光检查 SNL 大鼠受损 DRG 中磷酸化 AXL(p-AXL)和 AXL 的表达也受到抑制。此外,鞘内注射亚阈值剂量的 AXL 抑制剂 TP0903,显著延长单次 EA 治疗的镇痛时间,并增强重复 EA 治疗的镇痛效果,提示 EA 和 AXL 抑制剂具有协同作用。这些结果表明,AXL 信号在 EA 镇痛中起作用,AXL 抑制剂和 EA 的联合可能是神经性疼痛临床镇痛的新策略。

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