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

Xiao-Cui Yuan; Xiang-Ji Yan; Li-Xia Tian; Yi-Xiao Guo; Yu-Long Zhao; Sani Sa'idu Baba; Yu-Ying Wang; Ling-Li Liang; Hong Jia; Lin-Ping Xu; Li Li; Han Lin; Fu-Quan Huo

doi:10.3389/fnins.2021.733779

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

Front Neurosci. 2021 Sep 17:15:733779. doi: 10.3389/fnins.2021.733779. eCollection 2021.

Authors

Xiao-Cui Yuan^{1

2}, Xiang-Ji Yan^{1

2}, Li-Xia Tian^{1

2}, Yi-Xiao Guo^{1

2}, Yu-Long Zhao^{1

2}, Sani Sa'idu Baba^{1

2}, Yu-Ying Wang^{1

2}, Ling-Li Liang^{1

2}, Hong Jia^{1

2}, Lin-Ping Xu^{1

2}, Li Li³, Han Lin³, Fu-Quan Huo^{1

2}

Affiliations

¹ 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.
² Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
³ Key Laboratory of Anesthesiology of Zhejiang Province, Department of Anesthesiology, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.

Abstract

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-HT₁, 5-HT₂, and 5-HT₃ receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT₇ receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT₇ receptor is involved in EA analgesia. The 5-HT₇ 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-HT₇ receptor in the dorsal spinal cord. Intrathecal injection of 5-HT₇ receptor agonist AS-19 mimicked the analgesic effect of EA, while a selective 5-HT₇ 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-HT₇ 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.

Keywords: 5-HT7 receptor; GABAA receptor; chronic pain; electroacupuncture analgesia (EAA); knee osteoarthritis (KOA).