The selective blocker of voltage-gated sodium channels NaV1.7 PF-05089771 has the potential to inhibit cough in guinea pigs with allergic rhinitis

Allergic rhinitis (AR) is the most common cause of chronic cough which is a serious clinical problem. The cough hypersensitivity syndrome is associated with dysregulation of jugular C-fibres and nodose Aδ-fibres by inflammatory agents. Presently available antitussives have often limited efficacy, thus there is a continual demand for the development of novel more effective antitussives. Recent advances in the understanding of voltage-gated sodium channels (NaVs) have revealed that subtype NaV1.7 is involved in the initiation and conduction of cough and therefore presents a promising neural target. This study aimed to analyse the effect of NaV1.7 blocker PF-05089771 on cough in guinea pigs with AR. Animals sensitized by intraperitoneal ovalbumin (OVA) were intranasally challenged with OVA in 7-day intervals for 6 weeks. Cough was induced by inhalation of citric acid aerosol (0.4M) before nasal challenge (NCH) (baseline values), one hour after the 1^st, 3^rd, and 6^th NCH. On the 6^th NCH, the tested OVA group was pre-treated with an inhaled NaV1.7 blocker (PF-05089771, 100μM, 10min) before tussigen inhalation. Chronic AR significantly increased cough reflex to 0.4M citric acid compared to the control group (11.5±2.11 vs 5.9±1.20, P<0.05, n=9 for each group). Pre-treatment with the NaV1.7 blocker (PF-05089771, 100μM) resulted in significant inhibition of the cough reflex by ≈ 75% (2.7±0.75 vs 11.5±2.11, P<0.0001) without changes in respiratory rate. <bold>Conclusion:</bold> NaV1.7 blocker inhalation inhibited the stimulating effect of experimental allergic rhinitis on cough in awake guinea pigs. <italic>Supported by VEGA No. 1/0030/24 and APVV-22-0052.</italic>