Abstract

Background: The pathogenetic mechanisms of enhanced laryngeal reflex reactivity (ELRR) in patients with extraoesophageal reflux (EOR) are unclear. In a rat EOR model, a laryngeal acid-pepsin insult produces an ELRR that is mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by reactive oxygen species (ROS).

Aims: We investigated whether activation of P2X receptors by ATP subsequent to an increase in ROS may induce ELRR in an inflamed larynx that has been insulted by acid-pepsin or H₂O₂.

Subjects and Methods: The larynxes of 184 anesthetized rats were functionally isolated while the animals breathed spontaneously. Ammonia vapor was delivered into the larynx to measure laryngeal reflex reactivity.

Results: Laryngeal insult with acid-pepsin or H₂O₂ produced ELRR with similar characteristics. These two ELRR events were completely prevented by ATP scavengers (a combination of apyrase and adenosine deaminase) or a P2X receptor antagonist (iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate). Laryngeal application of a P2X receptor agonist (α,β-methylene-ATP) also produced ELRR. An insult with either acid-pepsin or H₂O₂ similarly promoted an increase in the levels of ATP, lipid peroxidation and inflammation in the larynx.

Conclusions: Laryngeal insult with acid-pepsin or H₂O₂ induces inflammation and produces excess ROS in the rat's larynx. The latter may in turn promote the release of ATP to activate P2X receptors resulting in sensitization of capsaicin-sensitive laryngeal afferent fibers and ELRR.