Transient receptor potential ion channel of the vanilloid type 1 (TRPV1)-dependent pathway, consisting of capsaicin-sensitive tachykininergic primary afferent and myenteric nitrergic neurons, was suggested to mediate the inhibitory effect of capsaicin on the vagally mediated striated muscle contractions in the rat esophagus. These primary afferent neurons upon entering into the esophagus are distributed through the myenteric plexus, terminating either in the myenteric ganglia or en route to the mucosa where they branch into a delicate net of fine varicose fibers. Therefore, this study aimed to investigate whether the mucosal primary afferents are a main mediator for the capsaicin inhibitory influence on vagally mediated contractions in the mouse esophagus. For this purpose, the vagally induced contractile activity of a thoracic esophageal segment was measured in the circular direction with a force transducer. Vagal stimulation (30 microsec, 25 V, 1-50 Hz for 1 sec) produced monophasic contractile responses, whose amplitudes were frequency-dependent. These contractions were completely abolished by d-tubocurarine (5 microM) while resistant to atropine (1 microM) and hexamethonium (100 microM). Capsaicin (30 microM) significantly inhibited the vagally induced contractions in esophagi with intact mucosa while its effect on preparations without mucosa was insignificant. Additionally, immunocytochemistry revealed the presence of TRPV1-positive nerve fibers in the tunica mucosa. Taken together, we conclude that in the mouse esophagus, capsaicin inhibits the vagally mediated striated muscle contractions mainly through its action on mucosal primary afferents, which in turn activate the presumed inhibitory local reflex arc.