VTA dopaminergic neurons involved in chronic spared nerve injury pain-induced depressive-like behavior

Affective disorders, such as depression, are commonly associated with the development of chronic pain, but the underlying mechanisms still remain unclear. The dopaminergic system, located in the midbrain, is considered one of the regions where algesia and emotional processing overlap. This suggests...

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Main Authors: Ludi Zhang, Menghan Ji, Yufei Sun, Qingwu Wang, Mingyang Jin, Shuling Wang, Hui Sun, Hailin Zhang, Dongyang Huang
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025000735
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author Ludi Zhang
Menghan Ji
Yufei Sun
Qingwu Wang
Mingyang Jin
Shuling Wang
Hui Sun
Hailin Zhang
Dongyang Huang
author_facet Ludi Zhang
Menghan Ji
Yufei Sun
Qingwu Wang
Mingyang Jin
Shuling Wang
Hui Sun
Hailin Zhang
Dongyang Huang
author_sort Ludi Zhang
collection DOAJ
description Affective disorders, such as depression, are commonly associated with the development of chronic pain, but the underlying mechanisms still remain unclear. The dopaminergic system, located in the midbrain, is considered one of the regions where algesia and emotional processing overlap. This suggests a structural basis hypothesis for the comorbidity of chronic pain and depression, highlighting the interplay between nociceptive and affective processing. But there are more and more evidences show that somatic and head/facial pain involve different neuronal overlap. In previous study, the research show that VTA dopaminergic system involved in pIONT surgery induced depressive-like behaviors in mice. But there still no evidence shows if chronic somatic pain will induce depressive-like behaviors and which neuronal circle pathway is underly. In this study, we assessed depressive-like behaviors and performed artificial interference of VTA (ventral tegmental area) dopaminergic neurons in a mouse model of chronic peripheral neuropathic pain induced by the spared nerve injury (SNI) model. After a 4-week duration of hyperalgesia and allodynia resulting from SNI surgery, social withdraw and other depressive-like behaviors were observed in the SNI group. Furthermore, the dopaminergic cells’ excitability in VTA were significantly increased in SNI mice. The excitability alteration was improved play a key role in the development and modulation of the chronic peripheral neuropathic pain-induced depressive-like behaviors. It has been shown pain and affections have structural and functional circuits to interact with each other, therefore the neuroplastic changes and functional role of VTA dopaminergic neurons within these circuits may serve as potential targets for understanding and therapeutically addressing the development of depressive-like symptoms accompanied by prolonged pain syndromes in humans.
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spelling doaj-art-cd273fe337ff45e89d515a36faf37d992025-08-20T02:47:21ZengElsevierBrain Research Bulletin1873-27472025-03-0122211126110.1016/j.brainresbull.2025.111261VTA dopaminergic neurons involved in chronic spared nerve injury pain-induced depressive-like behaviorLudi Zhang0Menghan Ji1Yufei Sun2Qingwu Wang3Mingyang Jin4Shuling Wang5Hui Sun6Hailin Zhang7Dongyang Huang8Department of Pharmacology; The Key Laboratory of Neural and Vascular Biology, Ministry of Education; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, 050017, Shijiazhuang, Hebei, PR China; College of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China; Identification Center of Forensic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, PR ChinaCollege of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, PR ChinaCollege of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, PR ChinaIdentification Center of Forensic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, PR ChinaIdentification Center of Forensic Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, PR ChinaThe First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR ChinaDepartment of Physiology, Binzhou Medical University, Yantai 264003, PR ChinaDepartment of Pharmacology; The Key Laboratory of Neural and Vascular Biology, Ministry of Education; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, 050017, Shijiazhuang, Hebei, PR ChinaDepartment of Pharmacology; The Key Laboratory of Neural and Vascular Biology, Ministry of Education; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, 050017, Shijiazhuang, Hebei, PR China; Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050000, PR China; Corresponding author at: Department of Pharmacology; The Key Laboratory of Neural and Vascular Biology, Ministry of Education; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, 050017, Shijiazhuang, Hebei, PR China.Affective disorders, such as depression, are commonly associated with the development of chronic pain, but the underlying mechanisms still remain unclear. The dopaminergic system, located in the midbrain, is considered one of the regions where algesia and emotional processing overlap. This suggests a structural basis hypothesis for the comorbidity of chronic pain and depression, highlighting the interplay between nociceptive and affective processing. But there are more and more evidences show that somatic and head/facial pain involve different neuronal overlap. In previous study, the research show that VTA dopaminergic system involved in pIONT surgery induced depressive-like behaviors in mice. But there still no evidence shows if chronic somatic pain will induce depressive-like behaviors and which neuronal circle pathway is underly. In this study, we assessed depressive-like behaviors and performed artificial interference of VTA (ventral tegmental area) dopaminergic neurons in a mouse model of chronic peripheral neuropathic pain induced by the spared nerve injury (SNI) model. After a 4-week duration of hyperalgesia and allodynia resulting from SNI surgery, social withdraw and other depressive-like behaviors were observed in the SNI group. Furthermore, the dopaminergic cells’ excitability in VTA were significantly increased in SNI mice. The excitability alteration was improved play a key role in the development and modulation of the chronic peripheral neuropathic pain-induced depressive-like behaviors. It has been shown pain and affections have structural and functional circuits to interact with each other, therefore the neuroplastic changes and functional role of VTA dopaminergic neurons within these circuits may serve as potential targets for understanding and therapeutically addressing the development of depressive-like symptoms accompanied by prolonged pain syndromes in humans.http://www.sciencedirect.com/science/article/pii/S0361923025000735Chronic peripheral neuropathic painDepressionVentral tegmental areaDopamine
spellingShingle Ludi Zhang
Menghan Ji
Yufei Sun
Qingwu Wang
Mingyang Jin
Shuling Wang
Hui Sun
Hailin Zhang
Dongyang Huang
VTA dopaminergic neurons involved in chronic spared nerve injury pain-induced depressive-like behavior
Brain Research Bulletin
Chronic peripheral neuropathic pain
Depression
Ventral tegmental area
Dopamine
title VTA dopaminergic neurons involved in chronic spared nerve injury pain-induced depressive-like behavior
title_full VTA dopaminergic neurons involved in chronic spared nerve injury pain-induced depressive-like behavior
title_fullStr VTA dopaminergic neurons involved in chronic spared nerve injury pain-induced depressive-like behavior
title_full_unstemmed VTA dopaminergic neurons involved in chronic spared nerve injury pain-induced depressive-like behavior
title_short VTA dopaminergic neurons involved in chronic spared nerve injury pain-induced depressive-like behavior
title_sort vta dopaminergic neurons involved in chronic spared nerve injury pain induced depressive like behavior
topic Chronic peripheral neuropathic pain
Depression
Ventral tegmental area
Dopamine
url http://www.sciencedirect.com/science/article/pii/S0361923025000735
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