Yuan Xiao-Cui, Yan Xiang-Ji, Tian Li-Xia, Guo Yi-Xiao, Zhao Yu-Long, Baba Sani Sa'idu, Wang Yu-Ying, Liang Ling-Li, Jia Hong, Xu Lin-Ping, Li Li, Lin Han, Huo Fu-Quan
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Institute of Neuroscience, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
Front Neurosci. 2021 Sep 17;15:733779. doi: 10.3389/fnins.2021.733779. eCollection 2021.
Knee osteoarthritis (KOA) is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT, 5-HT, and 5-HT receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT receptor is involved in EA analgesia. The 5-HT receptor is a stimulatory G-protein (Gs)-coupled receptor that activates adenylyl cyclase (AC) to stimulate cyclic adenosine monophosphate (cAMP) formation, which in turn activates protein kinase A (PKA). In the present study, we found that EA significantly increased the tactile threshold and the expression of the 5-HT receptor in the dorsal spinal cord. Intrathecal injection of 5-HT receptor agonist AS-19 mimicked the analgesic effect of EA, while a selective 5-HT receptor antagonist reversed this effect. Moreover, intrathecal injection of AC and PKA antagonists prior to EA intervention prevented its anti-allodynic effect. In addition, GABA receptor antagonist bicuculline administered (intrathecal, i.t.) prior to EA intervention blocked the EA effect on pain hypersensitivity. Our data suggest that the spinal 5-HT receptor activates GABAergic neurons through the Gs-cAMP-PKA pathway and participates in EA-mediated inhibition of chronic pain in a mouse model of KOA.
膝骨关节炎(KOA)是一种常见的致残性疾病,其特征为关节周围疼痛发作,是一种典型的慢性疼痛性疾病。先前的研究已证明,脊髓中的5 - HT、5 - HT和5 - HT受体参与电针(EA)镇痛。5 - HT受体在脊髓中发挥抗伤害感受作用。然而,尚不清楚5 - HT受体是否参与EA镇痛。5 - HT受体是一种刺激性G蛋白(Gs)偶联受体,可激活腺苷酸环化酶(AC)以刺激环磷酸腺苷(cAMP)形成,进而激活蛋白激酶A(PKA)。在本研究中,我们发现电针显著提高了触觉阈值以及背侧脊髓中5 - HT受体的表达。鞘内注射5 - HT受体激动剂AS - 19模拟了电针的镇痛效果,而选择性5 - HT受体拮抗剂则逆转了这种效果。此外,在电针干预前鞘内注射AC和PKA拮抗剂可预防其抗痛觉过敏作用。此外,在电针干预前鞘内注射GABA受体拮抗剂荷包牡丹碱可阻断电针对疼痛超敏反应的作用。我们的数据表明,脊髓5 - HT受体通过Gs - cAMP - PKA途径激活GABA能神经元,并参与电针介导的对KOA小鼠模型慢性疼痛的抑制作用。