Cough reflex induced by microinjection of citric acid into the larynx of guinea pigs: new coughing model.

We developed a new coughing model that evoked coughs by microinjection of citric acid into the larynx in unanesthetized unrestrained guinea pigs; additionally, we recorded synchronous sounds and waveforms of coughing utilizing built-in microphones and a whole body plethysmograph. The coughing model was able to distinguish a coughing response from other expiratory responses, such as an expiratory reflex or a sigh, by examining the waveform of the expiratory response and the existence of sound. It was not necessary to distinguish a cough from a sneeze, since the administration site was restricted to the larynx. Microinjection of 0.4 M citric acid, total of 20 microl (10 times, 2 microl at 30-s intervals), induced coughs (27.03 +/- 4.03 coughs in 10-min observation) that were stable and independent of the inhalation volume. In the inhalation studies, animals were exposed to citric acid only once, because the number of coughs remarkably decreased with repeated administration at intervals of 24 h (tachyphylaxis). However our coughing model was able to repeatedly challenge the microinjection of citric acid at an interval of 24 h. These results indicated that this coughing model was highly sensitive and correctly assessed the cough response.