Chronic cough is a significant problem, and in many patients
cough remains refractive to both disease-specific
therapies and current
cough-suppressing medicines, creating a need for improved
antitussive therapies. Most patients with
chronic cough also display heightened sensitivity so that they experience a persistent sense of the need to
cough, and often innocuous stimuli can trigger their coughing. This
hypersensitivity underpins the newly described concept of
cough hypersensitivity syndrome (CHS), a term that encapsulates the notion of common underlying mechanisms producing neuronal activation, sensitization and/or dysfunction, which are at the core of excessive coughing. Understanding these mechanisms has been a focus of recent research efforts in the field in the hope that new
therapies can be developed to selectively target sensitized unproductive
cough while maintaining the reflexive
cough essential for airway protection. However, efforts to achieve this have been slower than expected, in part because of some significant challenges and limitations translating current
cough models. In this review, we summarize recent advances in our understanding of the sensory circuits innervating the respiratory system that are important for
cough, how
cough sensory pathways become hypersensitive, and some of the recently described neural targets under development for treating
chronic cough. We present the case that better use of current
cough models or the development of new models, or both, is ultimately needed to advance our efforts to translate the discovery of basic
cough mechanisms into effective medicines for treating patients with
chronic cough.