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α7nAChR 在电针对神经损伤大鼠脊髓神经病理性疼痛的作用。

Involvement of α7nAChR in electroacupuncture relieving neuropathic pain in the spinal cord of rat with spared nerve injury.

机构信息

Department of Physiology, Gannan Medical University, Ganzhou, 341000, PR China.

Department of Physiology, Gannan Medical University, Ganzhou, 341000, PR China; Pain Medicine Research Insititute, Gannan Medical University, Ganzhou, 341000, PR China.

出版信息

Brain Res Bull. 2018 Mar;137:257-264. doi: 10.1016/j.brainresbull.2018.01.002. Epub 2018 Jan 4.

Abstract

Alpha-7 nicotinic acetylcholine receptor (α7nAChR) was reported to be involved in the modulation of neuropathic pain. Electroacupuncture (EA) has therapeutic effects on neuropathic pain induced by nerve injury, but the underlying mechanisms remain unclear. The present study was designed to investigate whether α7nAChR participates in the relieving effects of 2 Hz EA on neuropathic pain. Paw withdrawal threshold (PWT) was measured to study the EA-mediated analgesic effect in a rat model of spared nerve injury (SNI). The spinal α7nAChR and IL-1β expression levels were determined by RT-PCR, Western blot analysis, and immunofluorescence staining. Additionally, immunofluorescence targeting the expression of CD11b, which is a molecular indicator of microglial activation. The results showed that 2 Hz EA stimulation significantly improved the expression of α7nAChR and reduced the production of IL-1β and CD11b in the spinal cord of rats with SNI-induced neuropathic pain, along with the relief of mechanical hypersensitivity after EA treatment. Moreover, intrathecal injection of alpha-bungarotoxin (α-Bgtx), a selective antagonist for α7nAChR, at the dosage of 1.0 μg/kg, not only suppressed the analgesic effect of EA in SNI rats, but also inhibited the enhancement of α7nAChR expression and the reduction of IL-1β expression induced by EA. In conclusion, our study indicated that 2 Hz EA reduces SNI-induced mechanical hypersensitivity via upregulating α7nAChR and downregulating IL-1β and CD11b in the spinal cord of SNI rats, which might be one of the mechanisms underlying its effectiveness in the neuropathic pain.

摘要

α7 型烟碱型乙酰胆碱受体 (α7nAChR) 被报道参与神经病理性疼痛的调节。电针 (EA) 对神经损伤引起的神经病理性疼痛具有治疗作用,但具体机制尚不清楚。本研究旨在探讨 α7nAChR 是否参与 2 Hz EA 缓解神经病理性疼痛的作用。通过 spared nerve injury (SNI) 大鼠模型测量 paw withdrawal threshold (PWT) 来研究 EA 介导的镇痛作用。通过 RT-PCR、Western blot 分析和免疫荧光染色测定脊髓 α7nAChR 和 IL-1β 的表达水平。此外,通过免疫荧光检测 CD11b 的表达,CD11b 是小胶质细胞激活的分子指标。结果表明,2 Hz EA 刺激显著改善了 SNI 诱导的神经病理性疼痛大鼠脊髓中 α7nAChR 的表达,并降低了 IL-1β 和 CD11b 的产生,同时在 EA 治疗后缓解了机械性超敏反应。此外,鞘内注射α-银环蛇毒素(α-Bgtx),一种 α7nAChR 的选择性拮抗剂,剂量为 1.0 μg/kg,不仅抑制了 SNI 大鼠 EA 的镇痛作用,还抑制了 EA 诱导的 α7nAChR 表达增强和 IL-1β 表达降低。总之,我们的研究表明,2 Hz EA 通过上调 SNI 大鼠脊髓中的 α7nAChR 并下调 IL-1β 和 CD11b 来减轻 SNI 引起的机械性超敏反应,这可能是其在神经病理性疼痛中有效的机制之一。

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