Yuan Xiao-Cui, Zhu Bing, Jing Xiang-Hong, Xiong Li-Ze, Wu Cai-Hua, Gao Fang, Li Hong-Ping, Xiang Hong-Chun, Zhu He, Zhou Bin, He Wei, Lin Chuan-You, Pan Hui-Lin, Wang Qiang, Li Man
Department of Neurobiology and Key Laboratory of Neurological Diseases of Ministry of Education, The Institute of Brain Research, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
Front Mol Neurosci. 2018 Apr 6;11:112. doi: 10.3389/fnmol.2018.00112. eCollection 2018.
Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA) is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC) function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA). EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG) level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG) can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG)-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.
膝骨关节炎（KOA）是一种高度流行的慢性关节疾病，可导致慢性疼痛。尽管电针（EA）在临床上对缓解慢性疼痛有效，但其相关机制仍不清楚。弥漫性伤害性抑制控制（DNIC）功能降低与慢性疼痛有关，可能与内源性大麻素的作用有关。在本研究中，我们确定EA是否可能增强大麻素受体介导的下行抑制控制并抑制KOA小鼠模型中的慢性疼痛。我们发现抑制慢性疼痛的EA优化参数是低频高强度（2 Hz + 1 mA）。EA可逆转慢性疼痛时中脑CB1受体表达降低和2-花生四烯酸甘油（2-AG）水平降低的情况。向腹外侧导水管周围灰质（vlPAG）微量注射CB1受体拮抗剂AM251可逆转EA对疼痛超敏反应和DNIC功能的影响。此外，GABA能神经元而非谷氨酸能神经元上的CB1受体参与了EA对延髓中DNIC功能和5-HT下行抑制控制的影响，从而抑制慢性疼痛。我们的数据表明，内源性大麻素（2-AG）-CB1R-GABA-5-HT可能是参与EA改善DNIC功能和抑制慢性疼痛作用的一条新信号通路。
