Chronic Inflammatory Pain Impairs mGluR5-Mediated Depolarization-Induced Suppression of Excitation in the Anterior Cingulate Cortex
Chronic Inflammatory Pain Impairs mGluR5-Mediated Depolarization-Induced Suppression of Excitation in the Anterior Cingulate Cortex
复制标题
慢性炎症疼痛损害 mGluR5 介导的去极化诱导的前扣带皮层兴奋抑制
DOI：
10.1093/cercor/bhx117
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发表时间：
2018-06-01
期刊：
影响因子：
3.7
通讯作者：
Wu, Shengxi
中科院分区：
文献类型：
--
作者：
Guo, Baolin;Wang, Jiaqi;Wu, Shengxi
前扣带皮层（ACC）是伤害性知觉和疼痛相关焦虑的关键枢纽。ACC中的长时程突触可塑性被发现对慢性炎性疼痛和疼痛相关焦虑很重要。作为短时程突触可塑性，去极化诱导的兴奋抑制（DSE）与慢性应激、癫痫和自闭症等多种疾病有关。然而，它仍然是未知的，是否在ACC的DSE参与疼痛和焦虑的中枢敏化。采用全细胞膜片钳、钙离子成像、蛋白质印迹和行为学测试等方法，我们发现ACC突触后锥体细胞2s去极化可诱导DSE，DSE由内源性大麻素信号介导，并受代谢型谷氨酸受体5（mGluR5）调节。在完全弗氏佐剂诱导的炎性疼痛小鼠模型中，mGluR5的表达减少和功能障碍损害了DSE。CDPPB是一种mGluR5阳性变构调节剂，可在该疼痛模型中挽救超敏反应和焦虑样行为。我们的研究结果表明，mGluR5介导的ACC的短期可塑性可能是慢性疼痛的关键机制，mGluR5可能作为疼痛治疗的靶点，包括痛觉过敏和焦虑的治疗。
The anterior cingulate cortex (ACC) is a critical hub for nociceptive perception and pain-related anxiety. Long-term synaptic plasticity in ACC was found to be important for chronic inflammatory pain and pain-related anxiety. As short-term synaptic plasticity, depolarization-induced suppression of excitation (DSE) is involved in several conditions, such as chronic stress, epilepsy, and autism. However, it is still unknown whether DSE in the ACC is involved in the central sensitization of pain and anxiety. Using a whole-cell patch clamp, calcium imaging, western blot, and behavioral testing, we found that DSE was induced by a 2 s depolarization in postsynaptic pyramidal cells in ACC. DSE was mediated by endocannabinoid signaling and modulated by metabotropic glutamate receptor 5 (mGluR5). DSE was impaired by decreasing expression and dysfunction of mGluR5 in a mouse model of inflammatory pain induced by complete Freund's adjuvant. CDPPB, an mGluR5-positive allosteric modulator, could rescue hypersensitivity and anxiety-like behavior in this pain model. Our results demonstrated that mGluR5-mediated short-term plasticity in ACC may be a critical mechanism for chronic pain, and mGluR5 may potentially serve as a target of pain therapy, including treatments for hyperalgesia and anxiety.