ThermoTRP channels and beyond: mechanisms of temperature sensation

Patapoutian, Ardem; Peier, Andrea; Story, Gina M.; Viswanath, Veena

doi:10.1038/nrn1141

Cited by 731 publications

(559 citation statements)

References 109 publications

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“…Menthol's perceptual effects of cooling and sensory irritation have been well studied on the skin and in the mouth, 28,[37][38][39] and a recent investigation showed that menthol sniffed into the nose also produced burning and stinging as well as cooling. 40 Whereas menthol's innocuous cold sensations have been shown to depend on stimulation of the cold-sensitive receptor TRPM8, [41][42][43] its nociceptive sensations appear to arise at least in part from activation of the receptor TRPA1, 44,45 which plays an important role in pain perception, 46 including the sensitivity to painfully cold temperatures. 47 The data from experiment 1 show that when inhaled using the V2 E-cigarette, the coolness produced by 3.5% menthol was the most prominent flavor quality until the highest concentration of nicotine alone produced equal ratings of Overall Sensation.…”

Section: Discussionmentioning

confidence: 99%

Sensory Effects of Menthol and Nicotine in an E-Cigarette

Rosbrook

Green

2016

NICTOB

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Introduction: Despite the longstanding use and popularity of menthol as a flavorant in tobacco products, its sensory interactions with inhaled nicotine have never been measured independently of the other irritants in tobacco smoke. We therefore measured the perception of menthol in an E-cigarette with the primary goal of assessing its analgesic effect on the sensory irritation produced by inhaled nicotine. Methods: Adult cigarette smokers sampled aerosolized E-liquids containing five different concentrations of nicotine with 0%, 0.5%, or 3.5% l-menthol, as well as two commercial menthol flavors with and without nicotine. For each of the E-liquids participants used a labeled magnitude scale to rate the Overall Sensation intensity, Coolness/Cold, and Irritation/Harshness they experienced, and a Labeled Hedonic Scale to indicate how much they liked/disliked the overall flavor. Results: The main findings were that (1) perceived Irritation/Harshness was unaffected by a low (0.5%) menthol concentration, whereas a high menthol concentration (3.5%) led to higher perceived Irritation/Harshness at low nicotine concentrations but to lower Irritation/Harshness at the highest nicotine concentration (24 mg/ml); (2) a commercial Menthol-Mint flavor produced similar results; (3) nicotine tended to enhance rather than suppress sensations of Coolness/Cold; and (4) menthol tended to slightly increase liking independently of nicotine concentration. Conclusion: In addition to adding a sensation of coolness, menthol can reduce perceived airway irritation and harshness produced by inhalation when nicotine concentration is high, and contributes to the sensory impact of E-liquids when nicotine concentration is low. Implications: The evidence presented here indicates that menthol can potentially improve the appeal of E-cigarettes not only via its coolness and minty flavor, but also by reducing the harshness from high concentrations of nicotine. As the first direct demonstration of an analgesic effect of menthol on inhaled nicotine in humans, these data also have implications for the role of menthol flavors in other inhaled tobacco products.

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Section: Discussionmentioning

confidence: 99%

Sensory Effects of Menthol and Nicotine in an E-Cigarette

Rosbrook

Green

2016

NICTOB

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“…Based on their temperature responsiveness, TRPA1, TRPM8, TRPV1, TRPV2, TRPV3, and TRPV4 are also classified as thermal sensitive channels. The combined actions of these channels allow the body to distinguish a broad temperature range from <17°C to >52°C [2,3]. Among them, TRPV3 and TRPV4 are activated at temperatures higher than 33 and 27°C, respectively, implicating that they are activate, at least partially, at the normal body temperature of mammalian species.…”

Section: Introductionmentioning

confidence: 99%

The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active

Xiao¹,

Tian²,

Tang³

et al. 2008

Cell Calcium

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SummaryTRPV3 is a non-selective cation channel activated by warm to hot temperatures. In rodents, TRPV3 is highly expressed in basal keratinocytes of skin and oral/nasal epithelia. TRPV3 knockout mice showed impaired responses to innocuous and noxious heat but otherwise normal appearance and reactions to many sensory modalities. However, point mutations of TRPV3 at Gly573 to Ser and Cys have recently been linked to autosomal dominant hairless phenotypes and spontaneous dermatitis in mice and rats, implicating an important role for TRPV3 in alopecia and skin diseases. Exactly how the mutations affect TRPV3 function was unexplained. Here we show that both G573S and G573C mutations of murine TRPV3 are constitutively active in heterologous systems. In HEK293 cells, expression of the TRPV3 mutants causes cell death. In Xenopus oocytes, the constitutively active mutant channel is irresponsive to thermal and chemical stimuli but it reduces the temperature threshold and enhances the responses to heat and TRPV3 agonists of the wild type channel when they are co-expressed. We conclude that the G573S and G573C substitutions render the TRPV3 channel spontaneously active under normal physiological conditions, which in turn alters ion homeostasis and membrane potentials of skin keratinocytes, leading to hair loss and dermatitis-like skin diseases.

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“…Also, capsaicin, the primary pungent compound in hot pepper, evokes changes in [Ca 2ϩ ] i in sensory neurons by activation of the transient receptor potential vanilloid 1 (TRPV1) (15)(16)(17). These compounds, as well as other neurotransmitters and chemicals, have been shown to evoke intracellular acidification through an increase in [Ca 2ϩ ] i in sensory neurons (2,18).…”

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confidence: 99%