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The mechanism of this melatonin-induced esophagoprotection has not been clarified but it may be mediated, at least in part, by COX-PG and NOS-NO systems as well as the activation of sensory nerves because the pretreatment of animals with indomethacin, nonspecific blocker of COX-1/COX-2, L-NNA, a non-specific suppressor of the activity of NOS-NO system or capsaicin, a neurotoxin causing functional ablation of the afferent sensory nerves, significantly attenuated the preventive effects of melatonin on esophageal macroscopic lesions