2. Academic Validation
  3. The paraventricular thalamus mediates visceral pain and anxiety-like behaviors via two distinct pathways

The paraventricular thalamus mediates visceral pain and anxiety-like behaviors via two distinct pathways

  • Neuron. 2025 Jul 23;113(14):2310-2324.e7. doi: 10.1016/j.neuron.2025.04.019.
Di Li 1,  Yong-Chang Li 1,  Zheng-Yan Zhu 1,  Fu-Chao Zhang 1,  Qiu-Ying Zhao 1,  Jia-Hui Jiang 1,  Biyu Shen 2,  Yong Tang 3,  Guang-Yin Xu 4
Affiliations

Affiliations

  • 1 Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, Jiangsu, P.R. China.
  • 2 Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, Jiangsu, P.R. China; Department of Nursing, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University School of Nursing, Shanghai 200127, P.R. China.
  • 3 International Collaborative Centre on Big Science Plan for Purine Signaling, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan, P.R. China.
  • 4 Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, Jiangsu, P.R. China. Electronic address: guangyinxu@suda.edu.cn.
PMID: 40345185 DOI: 10.1016/j.neuron.2025.04.019
Abstract

Chronic visceral pain (CVP) often accompanies emotional disorders. However, the lack of suitable animal models has hindered research into their underlying molecular and neural circuitry mechanisms. Early-life stress is a key factor in developing both visceral hypersensitivity and emotional disorders, yet its pathological mechanisms are not well understood. This study showed that adult offspring of prenatal maternal stress (PMS)-exposed mice exhibited visceral hypersensitivity and anxiety-like behaviors. Glutamatergic neurons in the anterior paraventricular thalamus (aPVT) responded to visceral pain, while those in the posterior PVT (pPVT) were more responsive to anxiety. The aPVT-basolateral amygdala (BLA) and pPVT-central amygdala (CeA) circuits regulated CVP and anxiety, respectively. Notably, increased Cacna1e expression in aPVT enhanced both visceral pain and anxiety, while Grin2a upregulation in pPVT facilitated only anxiety. These findings highlight the distinct roles of aPVTGlu-BLAGlu-CeAGABA and pPVTGlu-CeAGABA circuits, providing insights for therapeutic approaches in CVP and anxiety comorbidity.

Keywords

anxiety; basolateral amygdala; central amygdaloid nucleus; chronic visceral pain; neural circuits; paraventricular thalamus nucleus.

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