[Coughing model by microinjection of citric acid into the larynx in guinea pig]

Many studies of cough were performed under the restrained or anesthetized condition, and coughs were evoked by inhalation of capsaicin or citric acid. Inhalation of irritants induced by "diving response" with apnea and coughs, and these responses induced a change of tidal volume. As a result, respiratory responses are dependent on the inhalation volume. Therefore we developed a new coughing model, and coughs were evoked by microinjection of citric acid into the larynx in the unanesthetized unrestrained guinea pig. Microinjection of 7.5% citric acid (2 microliters/30 s, 5 min) induced coughs (27.03 +/- 4.03 coughs/10 min), and citric acid-induced responses were stable independent of the inhalation volume. In the inhalation studies, animals were exposed to citric acid only once because induced-responses were remarkably decreased by repeated administration at an interval of 24 h. However in our coughing model it was possible to repeatedly challenge the animals by microinjection of citric acid at intervals of 24 h. Microinjection of citric acid into the larynx induced coughs in Sprague-Dawley rats, but inhalation of citric acid did not induce cough. These results indicate that this coughing model is highly sensitive and correctly assessed cough responses.