Dopaminergic neurons in the ventral periaqueductal gray projecting to the dorsal lateral septum regulate comorbid pain and anxiety

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-05-30 DOI:10.1016/j.brainresbull.2025.111409

Shaoshan Wang , Yani Guo , Bingdi Wei , Rukun Lu , Zhixuan Tan , Chaojun Wei

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引用次数: 0

Abstract

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.

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腹侧导水管周围灰质的多巴胺能神经元向背侧隔投射，调节共病性疼痛和焦虑。

疼痛和焦虑的共病是全球最普遍的精神健康障碍之一。然而，其潜在的病因机制仍不完全清楚。这项研究揭示了背外侧隔（LSD）及其相关的神经回路在疼痛和/或焦虑调节中起着关键作用。利用化学基因技术，我们发现LSD gaba能神经元的特异性抑制显著减轻了疼痛反应和焦虑样行为。相反，LSD gaba能神经元的特异性激活诱导小鼠痛觉过敏和焦虑样行为。此外，我们的研究表明，腹侧导水管周围灰质（vPAG）的多巴胺能神经元通过对LSD的投射在调节疼痛和焦虑共病中起着至关重要的作用。这种调节机制依赖于多巴胺的释放及其与LSD D2受体的结合。综上所述，本研究突出了LSD gaba能神经元及其相关神经回路在疼痛和焦虑共病中的重要作用，从而为开发潜在的治疗策略提供了新的理论基础和研究方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.