Potential Role of TRP Channels in Cough Hypersensitivity?

Cough is one of the commonest symptoms of medical importance. The mechanism whereby this protective reflex, vital for the integrity of the airway becomes excessively stimulated has recently been elucidated. The tickly sensation which provokes the urge to cough is invested in a series of nococeptors, which become upregulated in pathological states. In both acute and chronic cough, hypersensitivity to noxious stimuli can be objectively demonstrated. Members of a class of ion channels of the Transient Receptor Potential family act as irritant receptors responding to a wide variety of stimuli. The archetypal receptor, TRPV1 is stimulated by heat, acid, and the pungent extract of peppers, capsaicin. TRPV1 is upregulated by inflammatory mediators. Over expression and agonist induced increase in opening probability of the ion channel leads to increased sensitivity in the upper airway. The related TRPA1 is co-localised with TRPV1 and responds to a wide range of environmental stimuli through non-specific binding. It is likely that the combination of these two receptors is responsible for the almost universal complaint from patients with chronic cough of exquisite sensitivity to previously innocuous stimuli. The term, the Cough Hypersensitivity Syndrome has been coined to encapsulate the clinical manifestations of this up-regulation which occurs in the majority of patients presenting to the cough clinic.