Our previous study showed that silencing of lncRNA Gm14461 alleviated pain in a murine model of trigeminal neuralgia (TN), but the molecular mechanism remains not fully understood. Evidence indicates that astrocyte activation and autophagy are involved in the development of TN. Herein, this study aimed to elucidate whether the pain‐relief effect of Gm14461 silencing in TN involved regulation of astrocyte activation and autophagy. A murine model of TN was induced by chronic constriction injury of the infraorbital nerve surgery. The mechanical withdrawal threshold (MWT) was measured to assess the analgesic effect of Gm14461 silencing. Mouse astrocytes were treated with lipopolysaccharide (LPS) as a cell model. Astrocyte activation was evaluated by glial fibrillary acidic protein (GFAP) immunofluorescence and western blot analysis of GFAP. Autophagy was evaluated by LC3 immunofluorescence and western blot analysis of autophagy‐related proteins. The results showed that Gm14461 silencing increased MWT value in TN model mice. Meanwhile, Gm14461 silencing inhibited astrocyte activation and enhanced autophagy in both TN mice and LPS‐treated astrocytes. The enhancement of autophagy by Gm14461 silencing involved the activation of the AMPK signaling and the suppression of the Akt/mTOR signaling. Collectively, the analgesic effect of Gm14461 silencing in TN was related to attenuation of astrocyte activation via enhancement of autophagy.

中文翻译：

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lncRNA Gm14461的沉默通过抑制星形胶质细胞活化减轻三叉神经痛的疼痛

我们之前的研究表明，lncRNA Gm14461 的沉默减轻了三叉神经痛 (TN) 小鼠模型的疼痛，但其分子机制仍未完全了解。有证据表明星形胶质细胞活化和自噬参与了 TN 的发展。在此，本研究旨在阐明 Gm14461 沉默在 TN 中的镇痛作用是否涉及星形胶质细胞活化和自噬的调节。TN 的小鼠模型是由眶下神经手术的慢性收缩损伤诱导的。测量机械戒断阈值 (MWT) 以评估 Gm14461 沉默的镇痛效果。用脂多糖 (LPS) 作为细胞模型处理小鼠星形胶质细胞。通过胶质纤维酸性蛋白 (GFAP) 免疫荧光和 GFAP 的蛋白质印迹分析评估星形胶质细胞的活化。自噬通过 LC3 免疫荧光和自噬相关蛋白的蛋白质印迹分析进行评估。结果表明 Gm14461 沉默增加了 TN 模型小鼠的 MWT 值。同时，Gm14461 沉默抑制了 TN 小鼠和 LPS 处理的星形胶质细胞的星形胶质细胞活化并增强了自噬。Gm14461 沉默对自噬的增强涉及 AMPK 信号的激活和 Akt/mTOR 信号的抑制。总的来说，TN 中 Gm14461 沉默的镇痛作用与通过增强自噬减弱星形胶质细胞活化有关。Gm14461 沉默抑制了 TN 小鼠和 LPS 处理的星形胶质细胞的星形胶质细胞活化并增强了自噬。Gm14461 沉默对自噬的增强涉及 AMPK 信号的激活和 Akt/mTOR 信号的抑制。总的来说，TN 中 Gm14461 沉默的镇痛作用与通过增强自噬减弱星形胶质细胞活化有关。Gm14461 沉默抑制了 TN 小鼠和 LPS 处理的星形胶质细胞的星形胶质细胞活化并增强了自噬。Gm14461 沉默对自噬的增强涉及 AMPK 信号的激活和 Akt/mTOR 信号的抑制。总的来说，TN 中 Gm14461 沉默的镇痛作用与通过增强自噬减弱星形胶质细胞活化有关。