Perception of specific trigeminal chemosensory agonists

Abstract

The intranasal trigeminal system is a third chemical sense in addition to olfaction and gustation. As opposed to smell and taste, we still lack knowledge on the relationship between receptor binding and perception for the trigeminal system. We therefore investigated the sensitivity of the intranasal trigeminal system towards agonists of the trigeminal receptors TRPM8 and TRPA1 by assessing subjects’ ability to identify which nostril has been stimulated in a monorhinal stimulation design. We summed the number of correct identifications resulting in a lateralization score. Stimuli were menthol (activating TRPM8 receptors), eucalyptol (TRPM8), mustard oil (TRPA1) and two mixtures thereof (menthol/eucalyptol and menthol/mustard oil). In addition, we examined the relationship between intensity and lateralization scores and investigated whether intensity evaluation and lateralization scores of the mixtures show additive effects. All stimuli were correctly lateralized significantly above chance. Across subjects the lateralization scores for single compounds activating the same receptor showed a stronger correlation than stimuli activating different receptors. Although single compounds were isointense, the mixture of menthol and eucalyptol (activating only TRPM8) was perceived as weaker and was lateralized less accurately than the mixture of menthol and mustard oil (activating both TRPM8 and TRPA1) suggesting suppression effects in the former mixture. In conclusion, sensitivity of different subpopulations of trigeminal sensory neurons seems to be related, but only to a certain degree. The large coherence in sensitivity between various intranasal trigeminal stimuli suggests that measuring sensitivity to one single trigeminal chemical stimulus may be sufficient to generally assess the trigeminal system’s chemosensitivity. Further, for stimuli activating the same receptor a mixture suppression effect appears to occur similar to that observed in the other chemosensory systems.

Sex differences in chemosensation: sensory or emotional?

“…Two female participants did not participate in the ID test because they were highly familiar with the test and they had achieved high scores previously. Trigeminal sensitivity was assessed for the bimodal odor menthol with a 2-alternative, forced-choice, nostril-laterality detection threshold task using an ascending staircase with 5 reversals (Frasnelli et al, 2011a). For this, 16 concentrations of menthol (R.J. Reynolds Tobacco Company, CAS 2216-51-5, declared purity >99.97%), a bimodal odorant, ranging from 0.1 to 50% with each concentration reduced by one third, were prepared in propylene glycol (1,2 propanediol, Fisher Scientific, Acros Organics, CAS 57-55-6, declared purity >99%) and presented in 60 mL amber glass bottles.…”

“…Sensory sensitivity to menthol rather than to CO 2 or cineole, the two stimuli used in the EEG portion of the study, was assessed in order to avoid familiarization to one of the two stimulants. Recent findings suggest that sensitivity to menthol is highly correlated with sensitivity to cineole (Frasnelli et al, 2011a) leading us to believe that thresholds to menthol represent a valid measure of sensitivity to intranasal irritation in a broader sense.…”

The Development of a Menthol Solution for Use during Sport and Exercise

“…Perception may be dependent upon physiological factors such as trigeminal chemosensitivity [33,34] and stratum corneum thickness [35], or environmental influences such as previous or habitual exposure to trigeminal agonists [36,37], e.g., regular use of mentholated products. Habitual menthol use may alter the threshold at which TRPM8 channels and the trigeminal nerve are stimulated [37][38][39][40], ultimately habituating thermal sensation [37,38].…”

Trigeminal Chemesthesis

“…Under a dose-response approach, the eye irritation intensity produced by a mixture of 8 VOCs and two mixtures of 4 VOCs indicated that the components acted in a simple additive way to produce ocular irritation (Hempel-Jorgensen et al, 1999). A recent paper employed nasal lateralization scores and intensity ratings to compare 3 single chemicals (menthol, eucalyptol, and allyl isothiocyanate) and two mixtures (menthol/eucalyptol and menthol/allyl isothiocyanate) (Frasnelli et al, 2011a). Intensity ratings probably included odor plus chemesthesis (i.e., total nasal intensity), although it is not specifically stated.…”