Chronic cough pathophysiollogy: which mechanisms?

Introduction In some situations such as post-virus or post whooping cough, a non productive subacute cough may occur without apparent local inflammation, epithelium abnormalities or bronchoconstriction. This subacute or chronic cough represents a real syndrom (cough disease) due to the central nervous system (CNS) and its ortho and parasympathic outputs. At the CNS level, functional disturbancies and neosynaptogenesis can be described, with the intervention of the NMDA-type glutamatergic receptors. State of art The neurons located in the expiratory area of the breathing center (Pre-Boetzinger complex of the lower brainstem) present exagerated responses to stimuli, due to the repetitive stimulation of the NMDA receptors; this phenomenon is similar to long-term-potentiation (LTP), the molecular basis of learning, memory and neosynaptogenesis. The cough reflex is thus amplified and rapidly chronic and would justify any pharmacological intervention at the NMDA-receptors level. Perspectives More recently 5TH(4) receptors have been implied in the control of respiration; an overexpression of these receptors in the Pre-Boetzinger area could contribute to an increase of the cough reflex. Conclusion The present review aims at summarizing the main rationale target to pharmacologically block the chronic cough.