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

Proc Natl Acad Sci U S A. 2024 Mar 12;121(11):e2312136121. doi: 10.1073/pnas.2312136121. Epub 2024 Mar 6.

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 (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 pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Keywords: brain–body interactions; in vivo calcium imaging; neural circuits; pharyngeal inflammation–induced anxiety; quadruple trans-monosynaptic tracing.

MeSH terms

  • Animals
  • Anxiety
  • Brain
  • Humans
  • Inflammation
  • Mice
  • Pharyngitis*
  • Pharynx*
  • Sensory Receptor Cells