HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice
-
Published:2023-09-07
Issue:18
Volume:24
Page:13823
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Zheng Yawen1ORCID, Shao Shan1, Zhang Yu2, Yuan Shulu1, Xing Yuanwei1, Wang Jiaxin1, Qi Xuetao1ORCID, Cui Kun1, Tong Jifu1, Liu Fengyu1, Cui Shuang1, Wan You13ORCID, Yi Ming13
Affiliation:
1. Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China 2. National Health Commission Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS) & Peking Union Medical College (PUMC), Beijing 100101, China 3. Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100101, China
Abstract
Chronic pain is a significant health problem worldwide. Recent evidence has suggested that the ventral hippocampus is dysfunctional in humans and rodents, with decreased neuronal excitability and connectivity with other brain regions, parallel pain chronicity, and persistent nociceptive hypersensitivity. But the molecular mechanisms underlying hippocampal modulation of pain remain poorly elucidated. In this study, we used ex vivo whole-cell patch-clamp recording, immunofluorescence staining, and behavioral tests to examine whether hyperpolarization-activated cyclic nucleotide-gated channels 2 (HCN2) in the ventral hippocampal CA1 (vCA1) were involved in regulating nociceptive perception and CFA-induced inflammatory pain in mice. Reduced sag potential and firing rate of action potentials were observed in vCA1 pyramidal neurons from CFA-injected mice. Moreover, the expression of HCN2, but not HCN1, in vCA1 decreased in mice injected with CFA. HCN2 knockdown in vCA1 pyramidal neurons induced thermal hypersensitivity, whereas overexpression of HCN2 alleviated thermal hyperalgesia induced by intraplantar injection of CFA in mice. Our findings suggest that HCN2 in the vCA1 plays an active role in pain modulation and could be a promising target for the treatment of chronic pain.
Funder
National Natural Science Foundation of China National Key R&D Program of China Young Elite Scientists Sponsorship Program by CAST
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference62 articles.
1. Lipoxins and aspirin-triggered lipoxin inhibit inflammatory pain processing;Svensson;J. Exp. Med.,2007 2. Xiang, X., Wang, S., Shao, F., Fang, J., Xu, Y., Wang, W., Sun, H., Liu, X., Du, J., and Fang, J. (2019). Electroacupuncture stimulation alleviates CFA-induced inflammatory pain via suppressing P2X3 expression. Nat. Rev. Drug. Discov., 20. 3. Clinical presentation of patients suffering from recent onset chronic inflammatory back pain suggestive of spondyloarthritis: The DESIR cohort;Dougados;Joint. Bone. Spine.,2017 4. Effect and treatment of chronic pain in inflammatory arthritis;Lee;Curr. Rheumatol. Rep.,2013 5. Pain and Suffering;Siler;Semin. Oncol. Nurs.,2019
|
|