Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice

Yawen Zheng
ORCID logo ,
Shan Shao
,
Yu Zhang
,
Shulu Yuan
,
Yuanwei Xing
,
Jiaxin Wang
ORCID logo ,
Xuetao Qi
,
Kun Cui
,
Jifu Tong
,
Fengyu Liu
,
Shuang Cui
,
You Wan
,
Ming Yi
*
Version 1 : Received: 13 July 2023 / Approved: 18 July 2023 / Online: 18 July 2023 (10:11:02 CEST)

A peer-reviewed article of this Preprint also exists.

Zheng, Y.; Shao, S.; Zhang, Y.; Yuan, S.; Xing, Y.; Wang, J.; Qi, X.; Cui, K.; Tong, J.; Liu, F.; Cui, S.; Wan, Y.; Yi, M. HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice. Int. J. Mol. Sci. 2023, 24, 13823. Zheng, Y.; Shao, S.; Zhang, Y.; Yuan, S.; Xing, Y.; Wang, J.; Qi, X.; Cui, K.; Tong, J.; Liu, F.; Cui, S.; Wan, Y.; Yi, M. HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice. Int. J. Mol. Sci. 2023, 24, 13823.

Abstract

Chronic pain is a significant health problem worldwide. Recent evidence has suggested that dysfunctional states of the ventral hippocampus, including decreased neuronal excitability and connectivity with other brain regions, parallel pain chronicity and persistent nociceptive hypersensitivity in humans and rodents, respectively. 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 over-expression of HCN2 alleviated thermal hyperalgesia induced by intraplantar injection of CFA in mice. Our findings suggests that HCN2 in the vCA1 plays an active role in pain modulation and could be a promising target for the treatment of chronic pain.

Keywords

hyperpolarization-activated and cyclic nucleotide-gated channels; the ventral hippocampal CA1; nociceptive hypersensitivity; hippocampal neuronal excitability

Subject

Biology and Life Sciences, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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