Effect of topically applied menthol on thermal, pain and itch sensations and biophysical properties of the skin

The effect of menthol and alcohol as its vehicle on thermal sensations, pain, experimental itch and irritation were studied in 18 subjects, using a computerized thermal sensory analyzer, laser Doppler flowmetry and an evaporimeter for transepidermal water loss (TEWL). Menthol had a subjective cooling effect lasting up to 70 min in 12/18 subjects; however, it did not affect cold and heat threshold, nor did it affect cold and heat pain threshold. Alcohol produced an immediate cold sensation lasting up to 5 min in 4/18 subjects and lowered the sensitivity of cold sensation threshold (P < 0.05). Histamine injection did not change thermal and pain thresholds. Menthol did not alleviate histamine-induced itch magnitude, nor its duration. Following histamine injection, cold sensation median threshold decreased by 1.2 degrees C from (29.9 degrees C to 28.7 degrees C) on the site treated with menthol (P < 0.01) with similar changes in thresholds at the alcohol-treated site (P < 0.05). Warm sensation and pain threshold in subjects receiving histamine injections, measured after menthol and alcohol application, did not differ from their baseline values with histamine alone. TEWL at the site treated with menthol was significantly higher (P < 0.05) than at the alcohol-treated and the control site (P < 0.01), suggesting that menthol has a higher skin irritating effect, or at least alters the stratum corneum water permeability. Our results suggest that menthol fulfills the definition of a counterirritant, but does not affect histamine-induced itch, nor does it affect pain sensation.