Hypothalamic clock governs circadian pain

• 成果类型: Article
• 署名作者: Wei, Hong-Rui; Lou, Qianqian; Li, Le-Xian; Tang, Lan; Wu, Run-Jie; Li, Hong-Yu; Jiang, Ai-Jun; Yang, Xin-Lu; Gao, Wei; Zhao, Xin-Yi; Han, Liuhu; Mao, Yu; Qun, Sen; Luo, Yanli; Qian, Junchao; Jin, Yan; Zhang, Zhi
• 署名单位: Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Anhui Medical University; Anhui Medical University; Shanghai Jiao Tong University; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Anhui Medical University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.ady6455
• 发表日期: 2026-03-19
• 页码: eady6455
• 关键词: suprachiasmatic nucleus; paraventricular nucleus; spinal-cord; RAPID NEUROTRANSMISSION; SUBPARAVENTRICULAR ZONE; periaqueductal gray; LAMINAE I; neurons; rhythm; sleep

摘要

Chronic pain exhibits circadian rhythms in humans, but the mechanisms underlying such rhythmicity remain unclear. Here, we found daily oscillations in the nociceptive thresholds in a mouse model of neuropathic pain, driven by a rhythmic circuit from the master clock in the hypothalamus to the descending analgesia system. In the daytime (resting phase), higher vasoactive intestinal peptide (VIP) neuronal activity in suprachiasmatic nucleus (SCNVIP) activates a signaling pathway involving the paraventricular nucleus (PVN) and the ventrolateral periaqueductal gray (vlPAG), ultimately increasing nociceptive sensitivity. At night (active phase), reduced SCNVIP neuronal activity decreases pain sensitivity through this polysynaptic circuit. This study identified a circuit for regulating pain rhythmicity that might be targeted to improve chronic pain management.