HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice
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 hypersensiti...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/13823 |
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| author | Yawen Zheng Shan Shao Yu Zhang Shulu Yuan Yuanwei Xing Jiaxin Wang Xuetao Qi Kun Cui Jifu Tong Fengyu Liu Shuang Cui You Wan Ming Yi |
| author_facet | Yawen Zheng Shan Shao Yu Zhang Shulu Yuan Yuanwei Xing Jiaxin Wang Xuetao Qi Kun Cui Jifu Tong Fengyu Liu Shuang Cui You Wan Ming Yi |
| author_sort | Yawen Zheng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T22:41:36Z |
| format | Article |
| id | doaj.art-d445494aec344fcb93958012bceffea1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:41:36Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d445494aec344fcb93958012bceffea12023-11-19T11:03:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181382310.3390/ijms241813823HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in MiceYawen Zheng0Shan Shao1Yu Zhang2Shulu Yuan3Yuanwei Xing4Jiaxin Wang5Xuetao Qi6Kun Cui7Jifu Tong8Fengyu Liu9Shuang Cui10You Wan11Ming Yi12Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNational 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, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, ChinaChronic 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.https://www.mdpi.com/1422-0067/24/18/13823hyperpolarization-activated and cyclic nucleotide-gated channelsthe ventral hippocampal CA1nociceptive hypersensitivityhippocampal neuronal excitability |
| spellingShingle | Yawen Zheng Shan Shao Yu Zhang Shulu Yuan Yuanwei Xing Jiaxin Wang Xuetao Qi Kun Cui Jifu Tong Fengyu Liu Shuang Cui You Wan Ming Yi HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice International Journal of Molecular Sciences hyperpolarization-activated and cyclic nucleotide-gated channels the ventral hippocampal CA1 nociceptive hypersensitivity hippocampal neuronal excitability |
| title | HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice |
| title_full | HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice |
| title_fullStr | HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice |
| title_full_unstemmed | HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice |
| title_short | HCN2 Channels in the Ventral Hippocampal CA1 Regulate Nociceptive Hypersensitivity in Mice |
| title_sort | hcn2 channels in the ventral hippocampal ca1 regulate nociceptive hypersensitivity in mice |
| topic | hyperpolarization-activated and cyclic nucleotide-gated channels the ventral hippocampal CA1 nociceptive hypersensitivity hippocampal neuronal excitability |
| url | https://www.mdpi.com/1422-0067/24/18/13823 |
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