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

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 (NTSNE). These NTSNE 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-*NTSNE-*vBNST circuit can alleviate anxiety - like behaviors associated with pharyngeal inflammation. This study thus defines a pharynxto - brain axis that mechanistically links pharyngeal inflammation and emotional response. Significance Anxiety is an extremely common phenomenon among outpatients with pharyngitis, the latter of which is difficult to treat in the clinic. The relationship between anxiety and pharyngitis, as well as the neural circuit mechanisms potentially responsible for their comorbidity, have been all but ignored in research. Using extensive state - of- the - art tools and methods for neuroscience research, we identify a pharynxto - brain axis that primes pharyngeal inflammation- induced anxiety. This work defining a pharynxto - brain axis responsible for linking pharyngeal inflammation with anxiety via glossopharyngeal and vagal nerves holds major implications for expanding our understanding the connection between inflammation, sensory stimuli, and emotional response.