Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study

• Published in: Nicotine & tobacco research 2016-05, Vol.18 (5), p.596-603
• Main Authors: Nielsen, Thomas Arendt, Nielsen, Bruno Provstgaard, Wang, Kelun, Arendt-Nielsen, Lars, Boudreau, Shellie A.
• Format: Article
• Language: English
• Subjects: Adult; Blood Pressure - drug effects; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Female; Heart Rate - drug effects; Humans; Irritants; Male; Menthol - administration & dosage; Menthol - adverse effects; Mouth - blood supply; Mouth - drug effects; Nicotine - administration & dosage; Nicotine - adverse effects; Original Investigations; Pain - chemically induced; Pain Measurement; Pharynx - drug effects; Regional Blood Flow - drug effects; Thermosensing - drug effects; Tobacco Use Cessation Products - adverse effects; Tongue - blood supply; Tongue - drug effects; Young Adult
• ISSN: 1462-2203; 1469-994X
• DOI: 10.1093/ntr/ntv163

This study implemented an intra-oral test-platform to assess the sensory, psychophysical, and vasomotor responses to nicotine and menthol, alone or in combination. Two double-blinded, placebo-controlled, randomized, cross-over studies, including healthy nonsmoking participants were performed. Study I: A dose-response relationship (N = 20) between 0, 2, and 4 mg nicotine gum. Study II: An interaction response (N = 22) to 30 mg menthol and 4 mg nicotine alone or in combination. Heart rate, blood pressure, tactile and thermosensory thresholds, intra-oral blood flow and temperature, pain/irritation intensities/locations, McGill Pain Questionnaire, and taste experience were assessed before, during or after the completion of a standardized chewing regime. A dose-response elevation in heart rate was attenuated when nicotine was combined with menthol. Blood flow, temperature, and warm-detection thresholds, as assessed on the tongue, similarly increased for all gums. Pain intensity and taste experiences were similar between nicotine doses. Nicotine attenuated the sweet, cooling, and freshening sensation of menthol. Within the first 4 minutes, menthol reduced the intensity but not the area of nicotine-induced pain and irritation. The 4-mg nicotine dose led to a continued increase in the intensity and area of irritation in the throat post-chewing. Moreover, one-half of participants responded to menthol as an irritant, and these individuals demonstrated larger areas of nicotine-induced irritation in the throat post-chewing. The intra-oral test platform provides a basis to optimize the assessment of nicotine-related taste and sensory experiences and can be used in future studies for profiling nicotine gum.