Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells predominated allergic
inflammation in the esophagus and present with esophageal dysfunctions such as
dysphagia, food impaction, and
heartburn. However, the underlying mechanism of esophageal dysfunctions is unclear. This study aims to determine whether neurons in the vagal sensory ganglia are modulated in a guinea pig model of EoE. Animals were actively sensitized by
ovalbumin (OVA) and then challenged with
aerosol OVA inhalation for 2 wk. This results in a mild
esophagitis with increases in mast cells and eosinophils in the esophageal wall. Vagal nodose and jugular neurons were disassociated, and their responses to
acid,
capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist
AMG-9810 were studied by
calcium imaging and whole cell patch-clamp recording. Compared with naïve animals,
antigen challenge significantly increased
acid responsiveness in both nodose and jugular neurons. Their responses to
capsaicin were also increased after
antigen challenge.
AMG-9810, at a concentration that blocked
capsaicin-evoked
calcium influx, abolished the increase in
acid-induced activation in both nodose and jugular neurons.
Vagotomy strongly attenuated those increased responses of nodose and jugular neurons to both
acid and
capsaicin induced by
antigen challenge. These data for the first time demonstrated that prolonged
antigen challenge significantly increases
acid responsiveness in vagal nodose and jugular ganglia neurons. This sensitization effect is mediated largely through TRPV1 and initiated at sensory nerve endings in the peripheral tissues.
Allergen-induced enhancement of responsiveness to noxious stimulation by
acid in sensory nerve may contribute to the development of esophageal dysfunctions such as
heartburn in EoE.