The vagus nerve activated by inflammation co-transmits acute visceral pain via the NTS-PVN pathway

作者：Yu-Ting Zhao, Zi-Kun Zheng, Xia Yang, Yu-Juan Duan, X. Sunney Xie, Li Chen, Yan Xu, Yasi Zheng, Yanqiu Liu, Yong-yong Zhao, Xiao-Qing Tang, Jingming Shi, Jing-Dun Xie, Chuan Qin, Wen‐Jun Xin, Yue Wu, Jie Deng, Ting Xu · 发表于：Brain Behavior and Immunity · 年份：2026 · DOI：10.1016/j.bbi.2026.106551 · 被引用次数：2 · 研究领域：Vagus Nerve Stimulation Research、Gastrointestinal motility and disorders、Pain Mechanisms and Treatments

• A vagus-dependent pancreas-brain axis for inflammatory visceral pain is identified: TNF-α associated with acute pancreatitis sensitizes TRPV1 + vagal neurons and activates the NTS → PVN pathway. • Dual peripheral intervention strategies: Vagotomy (VGX) and nodose ganglion (NG) TRPV1 + neuron ablation (via RTX) both partially alleviate acute pancreatitis-induced pain, validating the vagus nerve as a critical pain conduit. • Central circuit-specific modulation: Chemogenetic or optogenetic inhibition of the NTS Glu → PVN Glu pathway attenuates visceral pain behaviors. Acute pancreatitis (AP) induces visceral pain through inflammation and mechanical stress, yet current treatments remain inadequate. This therapeutic limitation reflects our limited knowledge of how nociceptive signals are transmitted from peripheral visceral afferents to central neural pathways. A neural circuit connecting the pancreas and the brain was mapped using various viral tracer techniques. The role of this circuit in acute pancreatitis-induced visceral pain was verified using optogenetics, chemogenetics, fiber-optic in vivo calcium signal recording, and electrophysiological techniques. AP-associated elevation of the inflammatory cytokine TNF-α sensitizes transient receptor potential vanilloid 1-positive (TRPV1 + ) neurons in the nodose ganglia (NG) of the vagus nerve. Both bilateral subdiaphragmatic vagotomy (VGX) and NG resiniferatoxin (RTX) injection partially alleviated acute pancreatitis (AP)-induced...