Contribution of TRPM8‐mediated activity to thermally‐evoked reflex blink

Abstract

Purpose: To study the characteristics of reflex blink evoked by cold and heat stimulation of the ocular surface (OS), and to define the contribution of TRPM8 to the process.Methods: The orbicularis oculi muscle electromyography signal (OOemg) and the ocular surface temperature (OST; measured with a small thermoprobe placed on the cornea) were recorded in anaesthetised rats. OS temperature changes (ΔT) were induced by topical instillation of 20 μL drops of saline solution at different temperatures (15–50°C). ΔT and the area under the curve (AUC) and duration of the evoked OOemg signals were analysed before (control) and after topical treatment with the TRPM8 antagonist N‐(3‐aminopropyl)‐2‐[(3‐methylphenyl) methoxy] ‐N‐(2‐thienylmethyl) benzamide hydrochloride (AMTB; 1 mM).Results: Mild (−ΔT 0.1–5°C) and intense (−ΔT 5–15°C) cooling always evoked a reflex OOemg signal (probability = 1). AMTB significantly reduced the probability of cooling to evoke blink (probability = 0.26 and 0.57 for mild and intense cold stimuli, respectively; p < 0.001). OOemg AUC and duration were also significantly reduced by AMTB (p < 0.01). Probability of evoking OOemg signal by mild (ΔT 0.1–5°C) and intense (ΔT 5–15°C) OS heating was low (0.30 and 0.59 respectively), and their duration and AUC were significantly smaller than those evoked by cooling (p < 0.001). Although AMTB did not modify the probability of heating stimuli to evoke OOemg signals (0.17 and 0.57 for mild and intense heating, respectively), the duration of signals evoked by mild heating stimuli was significantly increased (p < 0.001).Conclusions: Cold stimuli applied to the ocular surface always evoked reflex EMG activity of the lid muscle. This ability of cooling stimuli to evoke reflex blink is mediated by TRPM8 channels, whose pharmacological blockade reduces both the probability to evoke the reflex blink and its amplitude.Support: PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103; CIPROM/2021/48 from Generalitat Valenciana, Spain.