Berberine alleviates chronic pain-induced anxiety-like behaviors by inhibiting the activation of VLT-projecting cACC (Cg2) neurons
Abstract Chronic pain is often accompanied by anxiety, and gradually increasing anxiety makes the pain itself more protracted. Berberine has been found to be able to cross the blood–brain barrier to treat psychiatric disorders, but its neurocirculatory mechanisms remain unclear. Here, we found that...
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Nature Portfolio
2024-12-01
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Series: | Communications Biology |
Online Access: | https://doi.org/10.1038/s42003-024-07372-2 |
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author | Min He Ye-Xiang Chen Pei-Pei Feng Jie Chen Chi Xu Shu-Ting Zhou Bo-Yu Liu Xiao-Fen He Xiao-Mei Shao Jian-Qiao Fang Zui Shen Jing-Gen Liu |
author_facet | Min He Ye-Xiang Chen Pei-Pei Feng Jie Chen Chi Xu Shu-Ting Zhou Bo-Yu Liu Xiao-Fen He Xiao-Mei Shao Jian-Qiao Fang Zui Shen Jing-Gen Liu |
author_sort | Min He |
collection | DOAJ |
description | Abstract Chronic pain is often accompanied by anxiety, and gradually increasing anxiety makes the pain itself more protracted. Berberine has been found to be able to cross the blood–brain barrier to treat psychiatric disorders, but its neurocirculatory mechanisms remain unclear. Here, we found that neurons in cingulate area 2 (Cg2) of the caudal anterior cingulate cortex (cACC), but not in Cg1 of the cACC, projected to the ventral lateral thalamus (VLT). Next, we induced chronic inflammatory pain by plantar injection of complete Freund’s adjuvant (CFA) and observed stable anxiety-like behaviors until two weeks postinjection. We specifically activated VLT-projecting cACC (Cg2) neurons in one-week-old CFA-induced mice without anxiety-like behaviors and in normal control mice to induce anxiety-like behaviors. We inhibited the activation of VLT-projecting cACC (Cg2) neurons in two-week-old CFA-treated mice with anxiety-like behaviors and observed that their anxiety-like behaviors were alleviated. On this basis, we further screened the effective dose of berberine for anxiolysis in two-week-old CFA-treated mice. We observed that the effective dose of berberine obtained above decreased the activity of VLT-projecting cACC (Cg2) neurons. The activation of VLT-projecting cACC (Cg2) neurons abrogated the anxiolytic effect of berberine in two-week-old CFA-treated mice. |
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institution | Kabale University |
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spelling | doaj-art-921e17e010b34e00899c1a13f73c0a152024-12-22T12:42:09ZengNature PortfolioCommunications Biology2399-36422024-12-01711910.1038/s42003-024-07372-2Berberine alleviates chronic pain-induced anxiety-like behaviors by inhibiting the activation of VLT-projecting cACC (Cg2) neuronsMin He0Ye-Xiang Chen1Pei-Pei Feng2Jie Chen3Chi Xu4Shu-Ting Zhou5Bo-Yu Liu6Xiao-Fen He7Xiao-Mei Shao8Jian-Qiao Fang9Zui Shen10Jing-Gen Liu11Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityDepartment of Acupuncture and Moxibustion, Tongde Hospital of Zhejiang ProvinceKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobilolgy and Acupuncture Reseach, The Third Affiliated Hospital of Zhejiang Chinese Medical UniversityAbstract Chronic pain is often accompanied by anxiety, and gradually increasing anxiety makes the pain itself more protracted. Berberine has been found to be able to cross the blood–brain barrier to treat psychiatric disorders, but its neurocirculatory mechanisms remain unclear. Here, we found that neurons in cingulate area 2 (Cg2) of the caudal anterior cingulate cortex (cACC), but not in Cg1 of the cACC, projected to the ventral lateral thalamus (VLT). Next, we induced chronic inflammatory pain by plantar injection of complete Freund’s adjuvant (CFA) and observed stable anxiety-like behaviors until two weeks postinjection. We specifically activated VLT-projecting cACC (Cg2) neurons in one-week-old CFA-induced mice without anxiety-like behaviors and in normal control mice to induce anxiety-like behaviors. We inhibited the activation of VLT-projecting cACC (Cg2) neurons in two-week-old CFA-treated mice with anxiety-like behaviors and observed that their anxiety-like behaviors were alleviated. On this basis, we further screened the effective dose of berberine for anxiolysis in two-week-old CFA-treated mice. We observed that the effective dose of berberine obtained above decreased the activity of VLT-projecting cACC (Cg2) neurons. The activation of VLT-projecting cACC (Cg2) neurons abrogated the anxiolytic effect of berberine in two-week-old CFA-treated mice.https://doi.org/10.1038/s42003-024-07372-2 |
spellingShingle | Min He Ye-Xiang Chen Pei-Pei Feng Jie Chen Chi Xu Shu-Ting Zhou Bo-Yu Liu Xiao-Fen He Xiao-Mei Shao Jian-Qiao Fang Zui Shen Jing-Gen Liu Berberine alleviates chronic pain-induced anxiety-like behaviors by inhibiting the activation of VLT-projecting cACC (Cg2) neurons Communications Biology |
title | Berberine alleviates chronic pain-induced anxiety-like behaviors by inhibiting the activation of VLT-projecting cACC (Cg2) neurons |
title_full | Berberine alleviates chronic pain-induced anxiety-like behaviors by inhibiting the activation of VLT-projecting cACC (Cg2) neurons |
title_fullStr | Berberine alleviates chronic pain-induced anxiety-like behaviors by inhibiting the activation of VLT-projecting cACC (Cg2) neurons |
title_full_unstemmed | Berberine alleviates chronic pain-induced anxiety-like behaviors by inhibiting the activation of VLT-projecting cACC (Cg2) neurons |
title_short | Berberine alleviates chronic pain-induced anxiety-like behaviors by inhibiting the activation of VLT-projecting cACC (Cg2) neurons |
title_sort | berberine alleviates chronic pain induced anxiety like behaviors by inhibiting the activation of vlt projecting cacc cg2 neurons |
url | https://doi.org/10.1038/s42003-024-07372-2 |
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