Purpose: To evaluate the role of transient receptor potential melastatin 8 (TRPM8) activity in menthol-induced cold sensitivity and its qualitative perception in patients with dry eye (DE). Methods: This prospective, cross-sectional, comparative study included 52 eyes of 52 subjects (mean age: 66.8 ± 9.2 years; range: 44–86) with a tear break-up time (TBUT) of ≤5 s. The participants were classified into three groups: 17 patients with DE symptoms and keratoconjunctival (KC) staining scores of ≥3 points (positive KC-DE group), 18 patients with DE symptoms and KC staining scores of <3 points (negative KC-DE group), and 17 individuals with KC staining scores of <3 points and no symptoms (non-DE control group). The menthol-induced cool sensation (M-cool) and TBUT were measured after administration of 2 μl of 1.0 mM menthol eye drops. Furthermore, participants answered a questionnaire regarding their stimulus perception (pleasant, unpleasant, or neither). Results: M-cool values were similar in the three groups. TBUT significantly increased in the negative KC-DE and control groups (P < 0.05) and remained unchanged in the positive KC-DE group (P > 0.05) after menthol administration. DE patients reported the sensation as pleasant or unpleasant, whereas most control participants were indifferent (P < 0.05). Conclusions: While M-cold sensitivity was similar in DE and control groups, its qualitative perception differed between these groups. Thus, TRPM8 activation at the peripheral level alone may not be sufficient to account for the manifestation of discomfort symptoms associated with DE.
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