title: Oral irritant properties of menthol: sensitizing and desensitizing effects of repeated application and cross-desensitization to nicotine.
abstract: The irritant properties of menthol and its interactions with nicotine were investigated psychophysically in human subjects. In the first experiment, 0.3% L-menthol was applied successively to one side of the tongue 10 times at a 1-min interval (30-s interstimulus interval, ISI), and subjects rated the intensity of the perceived irritation. The intensity of irritation progressively decreased across trials, consistent with desensitization. To test for cross-desensitization of nicotine-evoked irritation by menthol, nicotine (0.6%) was applied to both sides of the tongue simultaneously, 5 min after the conclusion of menthol application. Using both a two-alternative forced choice (2-AFC) paradigm, and also by obtaining independent ratings of the irritant intensity on each side of the tongue, it was found that nicotine-evoked irritation was significantly weaker on the menthol-pretreated side. To control for a possible confounding effect of cooling, nicotine was applied bilaterally only after the cooling sensation of menthol had subsided. Nicotine-induced irritation was still significantly weaker on the menthol-pretreated side, consistent with cross-desensitization of nicotine-evoked irritation by menthol. In a final experiment, menthol was repeatedly applied to one side of the tongue at a shorter (20 s) interval (5-s ISI), and elicited a rapid increase in irritant sensation over the initial trials, consistent with sensitization, followed in subsequent trials by a progressive reduction in irritation (desensitization). After a 5-min rest period, self-desensitization was confirmed. Repeated application of menthol at the same short ISI was then resumed, and resulted in a significant mean increase in irritant intensity consistent with stimulus-induced recovery (SIR).
authors.affiliation: Section of Neurobiology, Physiology and Behavior, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Dessirier
authors.forename: M
authors.initials: M
authors.lastname: O'Mahony
authors.forename: E
authors.initials: E
authors.lastname: Carstens
mesh_terms: D000293:Adolescent; D000328:Adult; D003887:Desensitization, Psychologic; D004347:Drug Interactions; D006801:Humans; D007509:Irritants / Q000494:pharmacology*; D008610:Menthol / Q000494:pharmacology*; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D011601:Psychophysics; D012684:Sensory Thresholds / Q000187:drug effects; D013823:Thermoreceptors / Q000187:drug effects*; D014059:Tongue / Q000294:innervation*; D014276:Trigeminal Nerve / Q000187:drug effects
chemical_list: D007509:Irritants; D008610:Menthol; D009538:Nicotine