Hu Xue-Fei, Zhang Hong, Yu Ling-Ling, Ge Wen-Qiang, Zhan-Mu Ou-Yang, Li Yan-Zhen, Chen Chao, Hou Teng-Fei, Xiang Hong-Chun, Li Yuan-Heng, Su Yang-Shuai, Jing Xiang-Hong, Cao Jie, Pan Hui-Lin, He Wei, Li Man
Department of Neurobiology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Pharmacol. 2022 Jul 8;13:919553. doi: 10.3389/fphar.2022.919553. eCollection 2022.
The therapeutic effects of electroacupuncture (EA) on the comorbidity of visceral pain and anxiety in patients with inflammatory bowel disease (IBD) is well known. It has been known that the ventral hippocampus (vHPC) and the cannabinoid type 1 receptors (CB1R) are involved in regulating anxiety and pain. Therefore, in this study, we determined whether EA reduces visceral pain and IBD-induced anxiety CB1R in the vHPC. We found that EA alleviated visceral hyperalgesia and anxiety in TNBS-treated IBD mice. EA reversed over-expression of CB1R in IBD mice and decreased the percentage of CB1R-expressed GABAergic neurons in the vHPC. Ablating CB1R of GABAergic neurons in the vHPC alleviated anxiety in TNBS-treated mice and mimicked the anxiolytic effect of EA. While ablating CB1R in glutamatergic neurons in the vHPC induced severe anxiety in wild type mice and inhibited the anxiolytic effect of EA. However, ablating CB1R in either GABAergic or glutamatergic neurons in the vHPC did not alter visceral pain. In conclusion, we found CB1R in both GABAergic neurons and glutamatergic neurons are involved in the inhibitory effect of EA on anxiety but not visceral pain in IBD mice. EA may exert anxiolytic effect downregulating CB1R in GABAergic neurons and activating CB1R in glutamatergic neurons in the vHPC, thus reducing the release of glutamate and inhibiting the anxiety circuit related to vHPC. Thus, our study provides new information about the cellular and molecular mechanisms of the therapeutic effect of EA on anxiety induced by IBD.
电针（EA）对炎症性肠病（IBD）患者内脏疼痛与焦虑共病的治疗作用已为人所知。已知腹侧海马体（vHPC）和1型大麻素受体（CB1R）参与调节焦虑和疼痛。因此，在本研究中，我们确定EA是否通过vHPC中的CB1R减轻内脏疼痛和IBD诱导的焦虑。我们发现EA减轻了经三硝基苯磺酸（TNBS）处理的IBD小鼠的内脏痛觉过敏和焦虑。EA逆转了IBD小鼠中CB1R的过表达，并降低了vHPC中表达CB1R的γ-氨基丁酸能神经元的百分比。消融vHPC中γ-氨基丁酸能神经元的CB1R可减轻经TNBS处理小鼠的焦虑，并模拟EA的抗焦虑作用。而消融vHPC中谷氨酸能神经元的CB1R则在野生型小鼠中诱发严重焦虑，并抑制EA的抗焦虑作用。然而，消融vHPC中γ-氨基丁酸能或谷氨酸能神经元的CB1R均未改变内脏疼痛。总之，我们发现γ-氨基丁酸能神经元和谷氨酸能神经元中的CB1R均参与EA对IBD小鼠焦虑的抑制作用，但不参与对内脏疼痛的抑制作用。EA可能通过下调γ-氨基丁酸能神经元中的CB1R并激活vHPC中谷氨酸能神经元中的CB1R来发挥抗焦虑作用，从而减少谷氨酸的释放并抑制与vHPC相关的焦虑回路。因此，我们的研究提供了关于EA对IBD诱导的焦虑治疗作用的细胞和分子机制的新信息。
