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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
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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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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