Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Previously, we developed a novel coughing model that evoked coughs via citric acid microinjection into the larynx of unanesthetized, unrestrained guinea pigs. Here, we compared the effects of capsaicin and citric acid administration into the larynx using this model. Inhalation of capsaicin (30 microM) or citric acid (0.4 M) for 5 min induced cough mimetic responses over a 10-min observation period (mean +/- S.E.M.: 8.85 +/- 1.60 and 10.40 +/- 1.17 coughs, respectively, n = 18). Microinjection of 0.4 M citric acid into the larynx (20 microl in total in 10 aliquots of 2 microl at 30-s intervals) induced 27.29 +/- 2.69 coughs over a 10-min observation period, whereas microinjection of 3 mM capsaicin evoked a maximum of 8.32 +/- 1.82 coughs (n = 18). Desensitization of C-fibers by capsaicin (100 mg/kg, s.c.) abolished the coughs evoked upon inhalation or microinjection of capsaicin and inhalation of citric acid, but had no significant effect on those induced by microinjection of citric acid. These results indicate that there were fewer non-myelinated C-fiber afferents in the larynx area than in other regions (bronchi or alveoli). Consequently, citric acid microinjected into the larynx may induce the cough reflex by stimulating other fibers (for example, Adelta-fibers), rather than C-fibers. In contrast, inhaled citric acid predominantly stimulated C-fibers, and hardly affected Adelta-fibers.