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  3. Reduced oxytocin signaling in the dBNST drives the transition from acute pain to persistent anxiety

Reduced oxytocin signaling in the dBNST drives the transition from acute pain to persistent anxiety

  • Curr Biol. 2025 Sep 26:S0960-9822(25)01182-0. doi: 10.1016/j.cub.2025.09.012.
Shunchang Fang 1,  Yuxin Qin 2,  Hanbing Lian 2,  Yufang Zhong 2,  Yishuai Yang 2,  Xiao-Dan Yu 2,  Shana Yang 3,  Jiankai Liang 2,  Wenhui Xiao 2,  Songhai Wen 2,  Xiao Min Zhang 2,  Boxing Li 4,  Lianyan Huang 5
Affiliations

Affiliations

  • 1 Joint Postdoctoral Research Station, Medical School of Jiaying University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong 514031, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Advanced Medical Technology Center, the First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, China.
  • 2 Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
  • 3 Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, Guangdong 510515, China.
  • 4 Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Advanced Medical Technology Center, the First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, China. Electronic address: liboxing@mail.sysu.edu.cn.
  • 5 Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Advanced Medical Technology Center, the First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou 510655, China. Electronic address: huangly55@mail.sysu.edu.cn.
PMID: 41015042 DOI: 10.1016/j.cub.2025.09.012
Abstract

Transient sensory experiences can trigger sustained emotional disturbances, yet the underlying neural mechanisms remain unclear. Here, we show that acute pain induces persistent anxiety in male mice, independent of ongoing nociceptive input, through reduced oxytocin signaling in the dorsal bed nucleus of the stria terminalis (dBNST). Reactivating oxytocin receptors (Oxtrs) in the dBNST markedly alleviated anxiety-like behaviors following pain resolution. Mechanistically, chemogenetic inhibition of somatostatin-expressing (SST) neurons in the dBNST (dBNSTSST neurons) abolished oxytocin's anxiolytic effects, while pharmacological blockade or selective knockdown of Oxtrs in these neurons increased anxiety-like behaviors. Transcriptomic and electrophysiological analyses further revealed that alterations in synaptic transmission and intrinsic excitability participate in this anxiety state. Together, these findings define a multilevel framework-spanning molecular, cellular, and circuit mechanisms-by which acute sensory input induces long-term emotional dysregulation. This study advances our understanding of pain-related affective disorders and highlights oxytocin signaling and dBNSTSST neurons as promising therapeutic targets.

Keywords

acute pain; dBNST; neuronal excitability; oxytocin; persistent anxiety; synaptic transmission.

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