Effectiveness of selective NaV1.7 blocker PF-05089771 in reducing cough associated with allergic rhinitis in guinea pigs.

Abstract

BACKGROUND: Allergic rhinitis (AR) is a common cause of chronic cough, linked to dysregulated airway C- and Aδ-fibres through inflammatory mediators. Despite the limited efficacy of current antitussive therapies, recent studies show that the Na1.7 inhibitor can block cough in naïve guinea pigs. This study aimed to analyse the effect of the Na1.7 blocker PF-05089771 on cough in guinea pigs with AR. METHODS: Dunkin Hartley guinea pigs were sensitised and challenged with ovalbumin (OVA). Cough was induced using citric acid aerosol (0.4 M) before nasal challenge (NCH), and then one hour after the 1st, 3rd, and 6th NCH. The OVA-inhibitor group was pre-treated with inhaled Na1.7 blocker (PF-05089771, 100 μM) before tussigen inhalation. RESULTS: Chronic AR increased cough response to citric acid in both males and females. Pre-treatment with Na1.7 blocker significantly inhibited cough reflex by ≈ 75 % in males and ≈ 80 % in females without affecting respiratory rate. CONCLUSION: Na1.7 blocker inhalation effectively inhibits cough in guinea pigs with AR.