Cough-Diversity and the peripheral mechanisms of production.

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Abstract
The physiology and pharmacology of the cough reflex were reviewed from the perspective that the cough response and its peripheral mechanisms have diversity, taking reported findings together with the results obtained from our own studies. It is clear that there was a remarkable difference in the magnitude of expiration and sound in coughing between the two types of coughs in guinea pigs: one is caused by mechanical irritation to the airway mucosa or citric acid inhalation and the other caused by inhalation of pharmacological agents such as capsaicin and substance P. Four types of stimulation, i.e., mechanical, physicochemical, chemical and pharmacological stimulation, were discussed with respect to the site and the mechanisms of action in the airway. Mechanical stimulants and chemical stimulants such as citric acid seem to act mainly on A delta-fibers. However, it is unclear whether pharmacological agents act on C-fibers to produce cough. As to the difference in distribution of cough receptors in the airway, pharmacological differences were found between coughs caused by mechanical irritation on the laryngeal sites and the site of bifurcation of the trachea. Furthermore, capsaicin, applied by a topical spraying method newly developed by us, produced cough-like forced expiration when it was sprayed around the site of the bifurcation of the trachea. This response was not depressed by codeine, but depressed by ophiopogonin, a Chinese herbal antitussive; mephenesine; and a neurokinin A antagonist. Mechanisms of cough augmentation in bronchitic guinea pigs were also described briefly. In conclusion, the site of action of cough stimulants and the mechanisms of cough production are still controversial. To solve these problems, we need to develop new methods and strategies for studying the cough reflex.

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