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To determine whether capsaicin-sensitive sensory nerves are involved in the swallowing reflex, we examined swallowing reflex in terms of the number of swallows elicited by injections of three different volumes (0.2, 0.4, and 0.6 ml) of distilled water, into the pharynx through a catheter in anesthetized guinea pigs pretreated with and without systemic capsaicin. The number of swallows was counted by submental electromyographic activity and visual observation of characteristic laryngeal movement. Injections of distilled water caused a volume-dependent increase in the number of swallows in animals treated with and without capsaicin. Capsaicin treatment significantly decreased the number of swallows elicited by all volumes of distilled water (p < 0.01). Exogenously administered substance P (SP) caused a dose-dependent increase in the number of swallows in all volumes but calcitonin gene-related peptide and acetylcholine were without effect. FK 888 (10(-5) M; 1 ml), a specific inhibitor of NK1 receptor, reduced the number of swallows elicited by distilled water to a similar degree as capsaicin treatment. Pharyngeal application of lidocaine (4%; 1 ml) also inhibited distilled water-induced swallowing. These results suggest that nonmyelinated C-fibers regulate the swallowing reflex through the release of SP in response to stimulation.