A pharynx-to-brain axis controls pharyngeal inflammation–induced anxiety

Author:

Zhao Wan1ORCID,Zhang Ke1,Dong Wan-Ying2,Tang Hao-Di23,Sun Jia-Qiang1,Huang Ji-Ye2,Wan Guang-Lun1,Guan Rui-Rui1,Guo Xiao-Tao1,Cheng Ping-Kai2,Tao Ran4,Sun Jing-Wu1,Zhang Zhi25,Zhu Xia2

Affiliation:

1. Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, People’s Republic of China

2. Department of Neurobiology and Biophysics, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, People’s Republic of China

3. Laboratory of Anesthesia and Critical Care Medicine Department of Anesthesia and Critical Care Laboratory, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China

4. Department of Vascular Surgery, The Second Hospital of Anhui Medical University, Hefei 230601, People’s Republic of China

5. The Center for Advanced Interdisciplinary Science and Biomedicine, Institute of Health and Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, People’s Republic of China

Abstract

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTS NE ). These NTS NE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTS NE →vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Funder

MOST | National Natural Science Foundation of China

MOST | National Key Research and Development Program of China

CAS Project for Young Scientists in Basic Research

the Institute of Health and Medicine

Plans for Major Provincial Science & Technology Projects

Natural Science Foundation of Anhui

Publisher

Proceedings of the National Academy of Sciences

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