5-HT7 Receptor Is Involved in Electroacupuncture Inhibition of Chronic Pain in the Spinal Cord

• Published in: Frontiers in neuroscience 2021-09, Vol.15, p.733779-733779
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 5-HT7 receptor; Acupuncture; Adenylate cyclase; Analgesia; Analgesics; Animals; Antibodies; Arthritis; Bicuculline; Biotechnology; Chronic pain; Cyclic AMP; Electroacupuncture; electroacupuncture analgesia (EAA); Fluorides; GABAA receptor; Hypersensitivity; Injection; Kinases; knee osteoarthritis (KOA); Ligaments; Neuroscience; Osteoarthritis; Pain; Pain perception; Polymerase chain reaction; Protein kinase A; Proteins; Serotonin receptors; Serotonin S1 receptors; Serotonin S2 receptors; Serotonin S3 receptors; Spinal cord; γ-Aminobutyric acid A receptors
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2021.733779

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 1 , 5-HT 2 , and 5-HT 3 receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT 7 receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT 7 receptor is involved in EA analgesia. The 5-HT 7 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 7 receptor in the dorsal spinal cord. Intrathecal injection of 5-HT 7 receptor agonist AS-19 mimicked the analgesic effect of EA, while a selective 5-HT 7 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 A 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 7 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.