Unveiling the etiology and the underlying mechanism of neuropathic pain, a poorly treated disease, is essential for the development of effective therapies. This study aimed to explore the role of mammalian target of rapamycin (mTOR) signaling in autophagy-mediated neuropathic pain. We established a spared nerve injury (SNI) model in adult male SD rats by ligating the common peroneal nerve and tibial, with the distal end cutoff. The paw withdrawal threshold (PWT) and C/A-fiber evoked field potentials were determined by electrophysiologic tests at day 0 (before operation), day 7 and day 14 postoperation, and SNI significantly increased field potentials (P < 0.05). Immunohistochemistry and western blots using spinal cord tissues showed that the expressions of GluR1, GluR2, Beclin-1, p62, mTOR and 4EBP1 were significantly increased after SNI (all P < 0.05), whereas the expressions of LC3 and LAMP2 were significantly decreased after SNI (all P < 0.05). Rapamycin efficiently counteracted the effect of SNI and restored the phenotypes to the level comparable to the sham control. In conclusion, rapamycin inhibits C/A-fiber-mediated long-term potentiation in the SNI rat model of neuropathic pain, which might be mediated by activation of autophagy signaling and downregulation of GluRs expression.

中文翻译：

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哺乳动物雷帕霉素信号通路靶标通过调节自噬参与脊髓背角突触可塑性和大鼠神经病理性疼痛。

神经性疼痛是一种治疗效果不佳的疾病，揭示其病因和潜在机制对于开发有效疗法至关重要。本研究旨在探讨哺乳动物雷帕霉素靶点（mTOR）信号在自噬介导的神经病理性疼痛中的作用。我们通过结扎腓总神经和胫骨，并切断远端，建立了成年雄性SD大鼠的备用神经损伤（SNI）模型。术后第0天（术前）、术后第7天和第14天通过电生理测试测定缩爪阈值（PWT）和C/A纤维诱发场电位，SNI显着增加场电位（P < 0.05）。脊髓组织免疫组化和Western blot结果显示，SNI后GluR1、GluR2、Beclin-1、p62、mTOR和4EBP1的表达显着升高（均P < 0.05），而LC3和LAMP2的表达显着降低。 （所有P<0.05）。雷帕霉素有效地抵消了 SNI 的影响，并将表型恢复到与假手术对照相当的水平。总之，雷帕霉素抑制 SNI 大鼠神经病理性疼痛模型中 C/A 纤维介导的长时程增强，这可能是通过激活自噬信号传导和下调 GluRs 表达来介导的。