Olfactory and trigeminal interaction of menthol and nicotine in humans

The purpose of the study was to investigate the interactions between two stimuli—menthol and nicotine—both of which activate the olfactory and the trigeminal system. More specifically, we wanted to know whether menthol at different concentrations modulates the perception of burning and stinging pain induced by nicotine stimuli in the human nose. The study followed an eightfold randomized, double-blind, cross-over design including 20 participants. Thirty phasic nicotine stimuli at one of the two concentrations (99 and 134 ng/mL) were applied during the entire experiment every 1.5 min for 1 s; tonic menthol stimulation at one of the three concentrations (0.8, 1.5 and 3.4 μg/mL) or no-menthol (placebo control conditions) was introduced after the 15th nicotine stimulus. The perceived intensities of nicotine’s burning and stinging pain sensations, as well as perceived intensities of menthol’s odor, cooling and pain sensations, were estimated using visual analog scales. Recorded estimates of stinging and burning sensations induced by nicotine initially decreased (first half of the experiment) probably due to adaptation/habituation. Tonic menthol stimulation did not change steady-state nicotine pain intensity estimates, neither for burning nor for stinging pain. Menthol-induced odor and cooling sensations were concentration dependent when combined with low-intensity nicotine stimuli. Surprisingly, this dose dependency was eliminated when combining menthol stimuli with high-intensity nicotine stimuli. There was no such nicotine effect on menthol’s pain sensation. In summary, we detected interactions caused by nicotine on menthol perception for odor and cooling but no effect was elicited by menthol on nicotine pain sensation

The Cellular Mechanism for Water Detection in the Mammalian Taste System

Initiation of drinking behavior relies on both internal state and peripheral water detection. While central neural circuits regulating thirst have been well studied, it is still unclear how mammals recognize external water. Here we show that acid-sensing taste receptor cells (TRCs) that were previously suggested as the sour taste sensors also mediate taste responses to water. Genetic silencing of these TRCs abolished water-evoked responses in taste nerves. Optogenetic self-stimulation of acid-sensing TRCs in thirsty animals induced robust drinking responses toward light even without water. This behavior was only observed when animals were water-deprived but not under food- or salt-depleted conditions, indicating that the hedonic value of water-evoked responses is highly internal-state dependent. Conversely, thirsty animals lacking functional acid-sensing TRCs showed compromised discrimination between water and nonaqueous fluids. Taken together, this study revealed a function of mammalian acid-sensing TRCs that provide a cue for external water

Nicotine activates the chemosensory cation channel TRPA1

8 pages, 7 figures.-- Supporting information available at: http://www.nature.com/neuro/journal/vaop/ncurrent/suppinfo/nn.2379_S1.htmlArticle in press.Topical application of nicotine, as used in nicotine replacement therapies, causes irritation of the mucosa and skin. This reaction has been attributed to activation of nicotinic acetylcholine receptors (nAChRs) in chemosensory neurons. In contrast with this view, we found that the chemosensory cation channel transient receptor potential A1 (TRPA1) is crucially involved in nicotine-induced irritation. We found that micromolar concentrations of nicotine activated heterologously expressed mouse and human TRPA1. Nicotine acted in a membrane-delimited manner, stabilizing the open state(s) and destabilizing the closed state(s) of the channel. In the presence of the general nAChR blocker hexamethonium, nociceptive neurons showed nicotine-induced responses that were strongly reduced in TRPA1-deficient mice. Finally, TRPA1 mediated the mouse airway constriction reflex to nasal instillation of nicotine. The identification of TRPA1 as a nicotine target suggests that existing models of nicotine-induced irritation should be revised and may facilitate the development of smoking cessation therapies with less adverse effects.K.T. and J.A.J.V. were supported by a postdoctoral mandate from KU Leuven and are currently postdoctoral fellows of the Research Foundation–Flanders (Fonds voor Wetenschappelijk Onderzoek, FWO). M.G. and W.E. are doctoral FWO fellows. V.M.M was supported by Spanish CONSOLIDER-INGENIO 2010 CSD2007-00023. This work was supported by grants from Inter-university Attraction Poles Programme (Belgian Science Policy, P6/28), FWO (G.0172.03 and G.0565.07), the Research Council of the KU Leuven (GOA 2004/07) and the Flemish Government (Excellentiefinanciering, EF/95/010).Peer reviewe