Dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxiety
The comorbidity of pain and anxiety is one of the most prevalent mental health disorders globally. However, its underlying etiological mechanisms remain incompletely understood. This study revealed that the dorsal lateral septum (LSD) and its associated neural circuits play key roles in pain and/or...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025002217 |
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| author | Shaoshan Wang Yani Guo Bingdi Wei Rukun Lu Zhixuan Tan Chaojun Wei |
| author_facet | Shaoshan Wang Yani Guo Bingdi Wei Rukun Lu Zhixuan Tan Chaojun Wei |
| author_sort | Shaoshan Wang |
| collection | DOAJ |
| description | The comorbidity of pain and anxiety is one of the most prevalent mental health disorders globally. However, its underlying etiological mechanisms remain incompletely understood. This study revealed that the dorsal lateral septum (LSD) and its associated neural circuits play key roles in pain and/or anxiety regulation. Using chemical genetic techniques, we found that the specific inhibition of LSD GABAergic neurons significantly alleviated pain responses and anxiety-like behaviors. Conversely, the specific activation of LSD GABAergic neurons induced hyperalgesia and anxiety-like behaviors in mice. Furthermore, our study showed that dopaminergic neurons in the ventral periaqueductal gray (vPAG) play a crucial role in regulating pain and anxiety comorbidity through their projections to the LSD. This regulatory mechanism depends on the release of dopamine and its binding to the D2 receptor of LSD. In summary, this study highlights the critical role of LSD GABAergic neurons and their associated neural circuits in the comorbidity of pain and anxiety, thereby providing a new theoretical foundation and research direction for developing potential therapeutic strategies. |
| format | Article |
| id | doaj-art-a89e7c104be1410d9e39744fde13e564 |
| institution | DOAJ |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-a89e7c104be1410d9e39744fde13e5642025-08-20T03:07:51ZengElsevierBrain Research Bulletin1873-27472025-08-0122811140910.1016/j.brainresbull.2025.111409Dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxietyShaoshan Wang0Yani Guo1Bingdi Wei2Rukun Lu3Zhixuan Tan4Chaojun Wei5School of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, ChinaSchool of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, ChinaSchool of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, ChinaSchool of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, ChinaSchool of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, ChinaSchool of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, China; NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, China; Institute of Clinical Research and Translational Medicine, Gansu Provincial Hospital, Lanzhou 730000, China; Corresponding author at: School of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, China.The comorbidity of pain and anxiety is one of the most prevalent mental health disorders globally. However, its underlying etiological mechanisms remain incompletely understood. This study revealed that the dorsal lateral septum (LSD) and its associated neural circuits play key roles in pain and/or anxiety regulation. Using chemical genetic techniques, we found that the specific inhibition of LSD GABAergic neurons significantly alleviated pain responses and anxiety-like behaviors. Conversely, the specific activation of LSD GABAergic neurons induced hyperalgesia and anxiety-like behaviors in mice. Furthermore, our study showed that dopaminergic neurons in the ventral periaqueductal gray (vPAG) play a crucial role in regulating pain and anxiety comorbidity through their projections to the LSD. This regulatory mechanism depends on the release of dopamine and its binding to the D2 receptor of LSD. In summary, this study highlights the critical role of LSD GABAergic neurons and their associated neural circuits in the comorbidity of pain and anxiety, thereby providing a new theoretical foundation and research direction for developing potential therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S0361923025002217Ventral periaqueductal grayDorsal lateral septumNeuropathic painD2 receptor |
| spellingShingle | Shaoshan Wang Yani Guo Bingdi Wei Rukun Lu Zhixuan Tan Chaojun Wei Dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxiety Brain Research Bulletin Ventral periaqueductal gray Dorsal lateral septum Neuropathic pain D2 receptor |
| title | Dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxiety |
| title_full | Dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxiety |
| title_fullStr | Dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxiety |
| title_full_unstemmed | Dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxiety |
| title_short | Dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxiety |
| title_sort | dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxiety |
| topic | Ventral periaqueductal gray Dorsal lateral septum Neuropathic pain D2 receptor |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025002217 |
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