Scientists have revealed the mechanism of how the TRPM8 sensor detects cold temperatures below 30°C and the cooling effect of menthol. TRPM8 is a polymodal ion channel that responds to cold and menthol both separately and together through overlapping but not identical pathways. Application of menthol shifts the activation threshold of the channel to warmer temperatures and increases its sensitivity, for example the EC50 of menthol is 60 μM at 20°C, which shifts 10-fold at 8°C. Studies in nerve cells have shown that 10–20% of ganglion neurons respond to cold with a threshold below 30°C and about 10% to cold stimuli around 20°C. Menthol induces calcium influx, membrane depolarization and generation of nerve impulses, while its effect is temperature-dependent and weakens above 37°C. These findings shed light on the molecular basis of the cool sensation and may inspire new treatments for pain and eye disorders.[1][2][3]