Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Neurosci Lett. 2021 Jan 19;743:135552. doi: 10.1016/j.neulet.2020.135552. Epub 2020 Dec 19.
Central sensitization is one of the important pathological mechanisms of chronic migraine (CM). Metabolic glutamate receptor 5 (mGluR5) mediates pain by activating various intracellular pathways. However, whether mGluR5 contributes to central sensitization in CM and the exact mechanism remains unclear. Male rats were used to establish a CM model by repeated infusions of inflammatory soup (IS) for 7 days to stimulate the activation of the dural nociceptor. The mechanical and thermal thresholds were used to evaluate allodynia, and central sensitization was assessed by measuring calcitonin gene-related peptide (CGRP) and substance P (SP). Microtubule associated protein 1 light chain 3 (LC3) and p62/SQSTM1 were used to assess autophagy. We found that the expression of mGluR5 in the trigeminal nucleus caudalis (TNC) of CM rats was significantly increased. In addition, the downregulation of mGluR5 activated autophagy by inhibiting the mTOR pathway. Moreover, the activation of autophagy alleviated allodynia and central sensitization in CM rats. This study identified a novel strategy for the treatment of CM; the downregulation of mGluR5 in a rat model of CM decreased the expression of the inflammatory factor interleukin-1 beta (IL-1β) and the central sensitization-associated proteins CGRP and SP by activating autophagy via inhibiting the mTOR pathway.
中枢敏化是慢性偏头痛（CM）的重要病理机制之一。代谢型谷氨酸受体 5（mGluR5）通过激活各种细胞内途径介导疼痛。然而，mGluR5 是否参与 CM 中的中枢敏化以及确切的机制尚不清楚。雄性大鼠通过重复输注炎症汤（IS）7 天来建立 CM 模型，以刺激硬脑膜伤害感受器的激活。使用机械和热阈值来评估痛觉过敏，通过测量降钙素基因相关肽（CGRP）和 P 物质（SP）来评估中枢敏化。微管相关蛋白 1 轻链 3（LC3）和 p62/SQSTM1 用于评估自噬。我们发现，CM 大鼠三叉神经尾核（TNC）中 mGluR5 的表达明显增加。此外，mGluR5 的下调通过抑制 mTOR 通路激活自噬。此外，自噬的激活减轻了 CM 大鼠的痛觉过敏和中枢敏化。这项研究确定了一种治疗 CM 的新策略；CM 大鼠模型中 mGluR5 的下调通过抑制 mTOR 通路激活自噬，降低了炎症因子白细胞介素-1β（IL-1β）和与中枢敏化相关的蛋白 CGRP 和 SP 的表达。
