Esophageal-tracheobronchial reflex is considered the main mechanism underlying
cough due to
gastroesophageal reflux, and is associated with esophageal
hypersensitivity. We hypothesized that tracheobronchial-esophageal reflex may also exist, and may be related to esophageal
hypersensitivity. To test this hypothesis, conscious and
ether-anesthetized guinea pigs were subjected to repetitive
capsaicin inhalation to establish models of
cough (conscious) and
cough-free (anesthetized) airway injury, respectively, followed by esophageal
acid infusion. Recurrent
capsaicin inhalation induced similar
cough hyperreactivity to inhaled
capsaicin after esophageal
acid infusion in guinea pigs with
cough and guinea pigs with
cough-free airway injury during recurrent
capsaicin inhalation.
Cough hyperreactivity, along with overexpression of transient receptor potential vanilloid 1 (TRPV1) receptors in esophageal mucosa and in nerve fibers of tracheal mucosa of guinea pigs were blocked by pretreatment with esophageal infusion of
capsazepine, but not
atropine. Thus, recurrent airway nociceptive stimuli induce esophageal hyperreactivity via a tracheobronchial-esophageal reflex mediated by vagal C afferents expressing TRPV1, and enhance
cough due to reflux.