Peripheral and central mechanisms of cough hypersensitivity

Chronic cough is a difficult to treat symptom of many respiratory and some non-respiratory diseases, indicating that varied pathologies can underpin the development of chronic cough. However, clinically and experimentally it has been useful to collate these different pathological processes into the single unifying concept of cough hypersensitivity. Cough hypersensitivity syndrome is reflected by troublesome cough often precipitated by levels of stimuli that ordinarily don’t cause cough in healthy people, and this appears to be a hallmark feature in many patients with chronic cough. Accordingly, a strong argument has emerged that changes in the excitability and/or normal regulation of the peripheral and central neural circuits responsible for cough are instrumental in establishing cough hypersensitivity and for causing excessive cough in disease. In this review, we explore the current peripheral and central neural mechanisms that are believed to be involved in altered cough sensitivity and present possible links to the mechanism of action of novel therapies that are currently undergoing clinical trials for chronic cough.