Fig. 4.

Time course of estimated mean values (19 participants) of odor, cooling and pain intensity estimates for menthol and placebo control. Thirty nicotine stimuli of low (99 ng/mL) and high (134 ng/mL) concentration were presented throughout the entire experimental session. Interstimulus interval: 1.5 min; total duration of experiment: 45 min. During the second half of each experimental session, an additional tonic menthol background stimulus was switched on (shadowed) and maintained throughout the rest of the experiment. Three concentrations of menthol (menthol-low: 0.8 μg/mL, menthol-medium: 1.5 μg/mL and menthol-high: 3.4 μg/mL) and a fourth condition with clean air (no menthol) as placebo control were combined with each of the two nicotine concentrations resulting in a total of eight experiments. Participants estimated the smell, cooling and pain sensation elicited by menthol separately on visual analog scales (VAS) after each nicotine stimulus. In the first half of the experiment, all estimates were close to zero. In the second half, estimates remained at this level for placebo control (no menthol), but increased to different levels after menthol was switched on. In the case of the high-nicotine condition, the odor and cooling estimates increased to the same level for all menthol concentrations (EU = estimation unit). The estimated mean values were derived from a linear mixed model for repeated measures using a least-square means statement