An increasing number of patients complain to medical institutions about a cough that persists for more than 8 weeks, namely chronic cough. The cough observed in patients with chronic cough is not responsive to conventional antitussive agents such as dihydrocodeine and dextromethorphan, and this is a major clinical problem. The most common pathology of chronic cough in Japan is dry cough. Two causes of dry cough are increased sensitivity of cough receptors (cough hypersensitivity) and increased contraction of bronchial smooth muscle. Among these, the mechanisms of cough hypersensitivity are diverse, and understanding these mechanisms is important for the diagnosis and treatment of chronic cough. In this paper I will review the regulatory mechanisms of cough hypersensitivity, especially the regulation of Aδ fiber excitability by C fibers. Furthermore, the central mechanisms involved cough reflex are discussed in relation to central acting antitussives.
Keywords: Aδ fiber; C fiber; P2X4 receptor; chronic cough; cough hypersensitivity; transient receptor potential vanilloid 1 (TRPV1).