Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic pain
Chronic pain caused by disease or injury affects more than 30% of the general population. The molecular and cellular mechanisms underpinning the development of chronic pain remain unclear, resulting in scant effective treatments. Here, we combined electrophysiological recording, in vivo two-photon (...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1140769/full |
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| author | Xiang-Jie Song Chen-Ling Yang Chen-Ling Yang Danyang Chen Yumeng Yang Yumeng Yang Yu Mao Peng Cao Aijun Jiang Wei Wang Zhi Zhang Wenjuan Tao Wenjuan Tao |
| author_facet | Xiang-Jie Song Chen-Ling Yang Chen-Ling Yang Danyang Chen Yumeng Yang Yumeng Yang Yu Mao Peng Cao Aijun Jiang Wei Wang Zhi Zhang Wenjuan Tao Wenjuan Tao |
| author_sort | Xiang-Jie Song |
| collection | DOAJ |
| description | Chronic pain caused by disease or injury affects more than 30% of the general population. The molecular and cellular mechanisms underpinning the development of chronic pain remain unclear, resulting in scant effective treatments. Here, we combined electrophysiological recording, in vivo two-photon (2P) calcium imaging, fiber photometry, Western blotting, and chemogenetic methods to define a role for the secreted pro-inflammatory factor, Lipocalin-2 (LCN2), in chronic pain development in mice with spared nerve injury (SNI). We found that LCN2 expression was upregulated in the anterior cingulate cortex (ACC) at 14 days after SNI, resulting in hyperactivity of ACC glutamatergic neurons (ACCGlu) and pain sensitization. By contrast, suppressing LCN2 protein levels in the ACC with viral constructs or exogenous application of neutralizing antibodies leads to significant attenuation of chronic pain by preventing ACCGlu neuronal hyperactivity in SNI 2W mice. In addition, administering purified recombinant LCN2 protein in the ACC could induce pain sensitization by inducing ACCGlu neuronal hyperactivity in naïve mice. This study provides a mechanism by which LCN2-mediated hyperactivity of ACCGlu neurons contributes to pain sensitization, and reveals a new potential target for treating chronic pain. |
| first_indexed | 2024-03-13T06:45:50Z |
| format | Article |
| id | doaj.art-b479ab4c5a5340ea952fc875565f4dea |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-03-13T06:45:50Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-b479ab4c5a5340ea952fc875565f4dea2023-06-08T06:09:22ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-06-011710.3389/fncel.2023.11407691140769Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic painXiang-Jie Song0Chen-Ling Yang1Chen-Ling Yang2Danyang Chen3Yumeng Yang4Yumeng Yang5Yu Mao6Peng Cao7Aijun Jiang8Wei Wang9Zhi Zhang10Wenjuan Tao11Wenjuan Tao12Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Oral Diseases Research of Anhui Province, College and Hospital of Stomatology, Anhui Medical University, Hefei, ChinaDepartment of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, ChinaHefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Oral Diseases Research of Anhui Province, College and Hospital of Stomatology, Anhui Medical University, Hefei, ChinaDepartment of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, ChinaHefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Neurology, Stroke Center, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaDepartment of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaHefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaKey Laboratory of Oral Diseases Research of Anhui Province, College and Hospital of Stomatology, Anhui Medical University, Hefei, ChinaDepartment of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, ChinaChronic pain caused by disease or injury affects more than 30% of the general population. The molecular and cellular mechanisms underpinning the development of chronic pain remain unclear, resulting in scant effective treatments. Here, we combined electrophysiological recording, in vivo two-photon (2P) calcium imaging, fiber photometry, Western blotting, and chemogenetic methods to define a role for the secreted pro-inflammatory factor, Lipocalin-2 (LCN2), in chronic pain development in mice with spared nerve injury (SNI). We found that LCN2 expression was upregulated in the anterior cingulate cortex (ACC) at 14 days after SNI, resulting in hyperactivity of ACC glutamatergic neurons (ACCGlu) and pain sensitization. By contrast, suppressing LCN2 protein levels in the ACC with viral constructs or exogenous application of neutralizing antibodies leads to significant attenuation of chronic pain by preventing ACCGlu neuronal hyperactivity in SNI 2W mice. In addition, administering purified recombinant LCN2 protein in the ACC could induce pain sensitization by inducing ACCGlu neuronal hyperactivity in naïve mice. This study provides a mechanism by which LCN2-mediated hyperactivity of ACCGlu neurons contributes to pain sensitization, and reveals a new potential target for treating chronic pain.https://www.frontiersin.org/articles/10.3389/fncel.2023.1140769/fullchronic painACCLCN2chemogeneticsneuronal hyperactivityin vivo 2P calcium imaging |
| spellingShingle | Xiang-Jie Song Chen-Ling Yang Chen-Ling Yang Danyang Chen Yumeng Yang Yumeng Yang Yu Mao Peng Cao Aijun Jiang Wei Wang Zhi Zhang Wenjuan Tao Wenjuan Tao Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic pain Frontiers in Cellular Neuroscience chronic pain ACC LCN2 chemogenetics neuronal hyperactivity in vivo 2P calcium imaging |
| title | Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic pain |
| title_full | Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic pain |
| title_fullStr | Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic pain |
| title_full_unstemmed | Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic pain |
| title_short | Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic pain |
| title_sort | up regulation of lcn2 in the anterior cingulate cortex contributes to neural injury induced chronic pain |
| topic | chronic pain ACC LCN2 chemogenetics neuronal hyperactivity in vivo 2P calcium imaging |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1140769/full |
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