Chronic cough is a common and persistent symptom of a number of chronic lung diseases or can also be idiopathic in origin, yet remains an unmet medical need. Cough is a reflex initiated following activation of airway sensory nerve terminals by various different exogenous and endogenous stimuli. Targeting this peripheral arm may uncover novel therapeutics. NaV1.7, a voltage gated sodium channel, is highly expressed on peripheral nerves, and is thought to be key to cough signal production and propagation. The aim of this study was to determine the effectiveness of a NaV1.7 inhibitor in blocking the various airway sensory nerves types thought to be involved in chronic coughing.

We utilised in vitro vagal sensory nerve tissue from the guinea pig (GP) and donor human lungs alongside in vivo electrophysiological and cough recordings in the GP.

A potent NaV1.7 antagonist caused concentration dependent inhibition of capsaicin induced depolarisation in the GP vagus, and also inhibited activation by a number of other tussive stimuli. Furthermore this compound inhibited activation of an isolated human vagus harvested from a subject with COPD. In vivo, when aerosolised, the NaV1.7 antagonist caused inhibition of both vagal A? and C-fibre firing (airway sensory fibre types responsible for the cough reflex) following activation by specific agonists along with significantly inhibiting induced cough in the whole animal.

These data indicate that a lung delivered NaV1.7 antagonist can inhibit sensory nerve activation irrespective of stimulus, or fibre type activated. NaV1.7 antagonists may therefore provide an effective treatment for cough through providing global inhibition of sensory nerve activation.