Evaluating the effects of A-803467, a selective NaV1.8 blocker, on cough response in guinea pigs with allergic rhinitis.

BACKGROUND

Airway sensory hypersensitivity contributes to enhanced cough reflex in allergic airway diseases. Voltage-gated sodium channel NaV1.8, expressed predominantly on nociceptive sensory neurons, may play a role in cough hypersensitivity. This study investigated the effect of repeated intranasal ovalbumin (OVA) challenge on citric acid-induced cough in guinea pigs and evaluated whether pretreatment with the selective NaV1.8 inhibitor A-803467 attenuates this response.

METHODS

Dunkin Hartley guinea pigs were sensitized and repeatedly challenged intranasally with OVA for six weeks. Citric acid-induced cough was assessed 1 h after the 1st, 4th, and 6th OVA challenge. Tested animals were pretreated with aerosolized A-803467 (3 mM) or vehicle for 10 min prior to and during citric acid exposure.

RESULTS

Repeated OVA challenge significantly increased citric acid-induced cough compared with controls. Pretreatment with inhaled A-803467 markedly suppressed cough (by approximately 70%) in both the 4th and 6th weeks of OVA challenge, without affecting respiratory rate.

CONCLUSION

Repeated allergen exposure enhances cough sensitivity, and inhibition of NaV1.8 effectively reduces cough in guinea pigs with allergic rhinitis. These findings suggest NaV1.8 as a potential therapeutic target for cough associated with allergic airway inflammation.