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J. Belmonte, S. Alfaro, T. B. Berenguer, J. M. Costa, V. Cuquerella, M. C. Acosta, C. Belmonte, J. Gallar; Effects of the TRPM8 Agonist Menthol on Corneal Sensitivity and Tear Secretion. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3405.
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To define the spontaneous and stimulus-evoked changes in corneal sensitivity following topical application of menthol.
Corneal esthesiometry was performed in 10 volunteers of both sexes (6 male, 4 female; 22±1 years), in 4 separate sessions using a Belmonte gas esthesiometer (Deriva Global SL, Spain), before and 30 min after application to one eye of a menthol solution (60µl; 1, 10 or 100µM menthol, and vehicle). The attributes of the sensation evoked by menthol (cooling, warmth, discomfort, irritation, burning, stinging, pricking, itching, tingling, numbing pain) were rated independently in 0-10 visual analogue scales (VAS). The Schirmer test was applied before and after menthol. For corneal sensation measurements, mechanical (air at 0-200ml/min flow), chemical (0%-80%CO2 in air at subthreshold flow) and cold (air at subthreshold flow reducing corneal temperature from -0.1º to -4.5ºC) stimuli were applied to the center of the cornea. After each stimulus, the magnitude of the intensity of the evoked sensation and of several of its psychophysical attributes (irritation, pricking, burning, warm, cold) was scored in separate VAS scales. Experiments were double-blinded.
After menthol instillation highest scores were given to irritation, cold, discomfort and stinging sensations.Intensity of the sensation evoked by corneal mechanical and chemical stimulation was not significantly modified by menthol, but perceived irritation was decreased, particularly after the highest menthol concentration. Intensity of the sensation evoked by cold stimulation was increased by menthol in a dose-dependent manner. Tear secretion was not modified by menthol application.
Mild irritation and discomfort were the main spontaneous sensation parameters evoked by topical application of menthol to the eye. In addition, menthol attenuated the irritation sensations evoked by mechanical and chemical stimulation of the cornea and enhanced intensity of the sensation evoked by cold. This possibly reflects an increase by menthol of spontaneous and stimulus-evoked activity in cold receptor fibers and a partial desensitization of nociceptors, and suggest that augmented cold receptor activity evokes conscious sensations with an unpleasant component.
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