ReviewRole of reactive oxygen species and TRP channels in the cough reflex

- Cough is triggered by the activation of specific airway afferent subtypes.
- ROS cause activation of airway C fibers via TRPA1.
- ROS increase the excitability of airway C fibers through multiple mechanisms.

The cough reflex is evoked by noxious stimuli in the airways. Although this reflex is essential for health, it can be triggered chronically in inflammatory and infectious airway disease. Neuronal transient receptor potential (TRP) channels such as ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are polymodal receptors expressed on airway nociceptive afferent nerves. Reactive oxygen species (ROS) and other reactive compounds are associated with inflammation, from either NADPH oxidase or mitochondria. These reactive compounds cause activation and hyperexcitability of nociceptive afferents innervating the airways, and evidence suggests key contributions of TRPA1 and TRPV1.