Cough is a natural response to remove irritants, foreign bodies, mucus, and pathogens from the respiratory tract. The cough response is controlled by the nervous system, and when irritants are sensed in the airways by nerve fibers, signals are sent to the brain’s cough center. In turn, the brain sends signals to effector muscles to cue the upper body to cough.1

Nerve Dysfunction Contributes to Refractory Chronic Cough1

It has been observed in patients with refractory chronic cough that the density of sensory nerves is increased in the airways2, the expression of nerve proteins is altered1 and the nerves controlling cough become more excitable.3

P2X3 Receptors and Refractory Chronic Cough

P2X3 receptors are found on airway nerve fibers responsible for signaling the urge to cough.4

1. Chung et al, (2013) Lancet Respir Med 1(5):414-22. 2. Shapiro et al. (2021) Am J Respir Crit Care Med 203(3):348-355. 3. Hilton et al. (2013) J Allergy Clin Immunol 132(4):847-55.e1-5. 4. Kamei et al. (2005) Eur J Pharmacol. 28;528(1-3):158-61. 5. Garceau et al. (2019) Pulm Pharmacol Ther 56:56-62. 6. Abdulqawi et al. (2015) Lancet 385(9974):1198-205. 7. Smith et al. (2022) Am J Respir Crit Care Med 205:A5778