Involvement of capsaicin-sensitive nerves in the initiation of swallowing evoked by carbonated water in anesthetized rats.

Capsaicin powerfully evokes the swallowing reflex and is a known therapeutic agent for improving dysphagia and preventing aspiration pneumonia. However, the role of capsaicin-sensitive nerves in the initiation of swallowing evoked by various natural stimuli remains unclear. To explore this question, we blocked laryngeal capsaicin-sensitive nerves following the coapplication of QX-314 and capsaicin (QX/Cap), and investigated the effects on swallowing evoked by mechanical and chemical stimulation in anesthetized rats. Swallows were evoked by capsaicin, carbonated water (CW), distilled water (DW), and punctate mechanical stimulation using von Frey filaments applied topically to the larynx. Swallows were documented by recording electromyographic activation of the suprahyoid and thyrohyoid muscles. The initiation of swallowing by capsaicin was strongly suppressed at 5 min following QX/Cap treatment and returned in a time-dependent manner. CW-evoked swallows at 5 min following QX/Cap treatment were significantly diminished compared with before and 30 min after treatment. In contrast, DW-evoked and mechanically evoked swallows were unchanged by QX/Cap treatment. Furthermore, CW-evoked swallows were virtually abolished by transection of the superior laryngeal nerves and significantly decreased by the topical application of acid-sensing ion channel-3 (ASIC3) inhibitor APETx2, but they were not affected by the nonselective transient receptor potential channel inhibitor ruthenium red or the ASIC1 inhibitor mambalgin-1. Taken together, we speculate that capsaicin-sensitive nerves play an important role in the initiation of CW-evoked swallows. The initiation of swallowing evoked by laryngeal capsaicin and carbonated water application was diminished by the coapplication of QX-314 and capsaicin. Carbonated water-evoked swallows were also abolished by transection of the superior laryngeal nerves and were inhibited by the acid-sensing ion channel-3 inhibitor. Capsaicin-sensitive nerves are involved in the initiation of carbonated water-evoked swallows.