TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol

Namer, Barbara; Seifert, F.; Handwerker, Hermann O.; Maihöfner, Christian

doi:10.1097/00001756-200506210-00015

Cited by 225 publications

(238 citation statements)

References 23 publications

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“…It is thus possible that vascular responses to these agonists in the current study could be mediated, at least partially, via TRPA1 channels. However, as specific activation of TRPM8 and TRPA1 channels has different vascular effects in human forearm skin (25), it seems unlikely that our responses in either the rat or human study were mediated by TRPA1 channels. Additionally, to date no study has reported the presence of TRPA1 channels in vascular tissues.…”

Section: Discussionmentioning

confidence: 92%

“…In contrast, control of the human forearm cutaneous circulation is more complex, having all of these elements active, in addition to sympathetic vasoconstrictor tone (15,17,19,25,33). It is possible that neuronal activation by TRPM8 channels may result in a vasodilatation.…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that neuronal activation by TRPM8 channels may result in a vasodilatation. A recent study (25) used this vascular bed as a model to investigate sensory actions of menthol and other TRP channel agonists. They reported that although menthol caused vasodilatation at the site of application, it was localized to this area alone, implying that menthol did not evoke a sensory axon reflex to cause the release of vasodilator substances remote from the site of application, whereas TRPA1 channel agonism did.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

Johnson¹,

Melanaphy²,

Purse³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

136

137

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Johnson CD, Melanaphy D, Purse A, Stokesberry SA, Dickson P, Zholos AV. Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone. Am J Physiol Heart Circ Physiol 296: H1868 -H1877, 2009. First published April 10, 2009 doi:10.1152/ajpheart.01112.2008.-The transient receptor potential melastatin 8 (TRPM8) channel has been characterized as a cold and menthol receptor expressed in a subpopulation of sensory neurons but was recently identified in other tissues, including the respiratory tract, urinary system, and vasculature. Thus TRPM8 may play multiple functional roles, likely to be in a tissue-and activation statedependent manner. We examined the TRPM8 channel presence in large arteries from rats and the functional consequences of their activation. We also aimed to examine whether these channels contribute to control of conscious human skin blood flow. TRPM8 mRNA and protein were detected in rat tail, femoral and mesenteric arteries, and thoracic aorta. This was confirmed in single isolated vascular myocytes by immunocytochemistry. Isometric contraction studies on endothelium-denuded relaxed rat vessels found small contractions on application of the TRPM8-specific agonist menthol (300 M). However, both menthol and another agonist icilin (50 M) caused relaxation of vessels precontracted with KCl (60 mM) or the ␣-adrenoceptor agonist phenylephrine (2 M) and a reduction in sympathetic nerve-mediated contraction. These effects were antagonized by bromoenol lactone treatment, suggesting the involvement of Ca 2ϩ -independent phospholipase A 2 activation in TRPM8-mediated vasodilatation. In thoracic aorta with intact endothelium, menthol-induced inhibition of KCl-induced contraction was enhanced. This was unaltered by preincubation with either N -nitro-L-arginine methyl ester (L-NAME; 100 nM), a nitric oxide synthase inhibitor, or the ACh receptor antagonist atropine (1 M). Application of menthol (3% solution, topical application) to skin caused increased blood flow in conscious humans, as measured by laser Doppler fluximetry. Vasodilatation was markedly reduced or abolished by prior application of L-NAME (passive application, 10 mM) or atropine (iontophoretic application, 100 nM, 30 s at 70 A). We conclude that TRPM8 channels are present in rat artery vascular smooth muscle and on activation cause vasoconstriction or vasodilatation, dependent on previous vasomotor tone. TRPM8 channels may also contribute to human cutaneous vasculature control, likely with the involvement of additional neuronal mechanisms.human; rat; artery ION CHANNELS, ESPECIALLY Ca 2ϩ -permeable channels, are of central importance to the control of vascular tone as well as long-term phenotypic remodeling. In recent years, members of the transient receptor potential (TRP) superfamily of cation channels attracted considerable interest as novel nonvoltage gated Ca 2ϩ permeable cation channels, important determinants of vascular function and disease (2, 4, 5, 13). These channels can be constitutively active or acti...

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

Johnson¹,

Melanaphy²,

Purse³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

136

137

View full text Add to dashboard Cite

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“…(See, however, Kobayashi et al 2005. ) Studies have also shown that menthol can evoke nociceptive sensations (Green 1992;Cliff and Green 1994;Namer et al 2005) via stimulation of C-fibers (Wasner et al 2004). LTN sites and spots may therefore be attributable to primary afferent fibers that express TRPV1 together with TRPV3 or TRPM8..…”

Section: Discussionmentioning

confidence: 99%

Nociceptive sensations evoked from ‘spots’ in the skin by mild cooling and heating

Green

Roman

Schoen

et al. 2008

Pain

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It was recently found that nociceptive sensations (stinging, pricking, or burning) can be evoked by cooling or heating the skin to innocuous temperatures (e.g., 29°, 37°C). Here we show that this lowthreshold thermal nociception (LTN) can be traced to sensitive 'spots' in the skin equivalent to classically defined warm spots and cold spots. Because earlier work had shown that LTN is inhibited by simply touching a thermode to the skin, a spatial search procedure was devised that minimized tactile stimulation by sliding small thermodes (16 mm 2 and 1 mm 2 ) set to 28° or 36°C slowly across the lubricated skin of the forearm. The procedure uncovered three types of temperature-sensitive sites (thermal, bimodal and nociceptive) that contained one or more thermal, nociceptive or (rarely) bimodal spots. Repeated testing indicated that bimodal and nociceptive sites were less stable over time than thermal sites, and that mechanical contact differentially inhibited nociceptive sensations. Intensity ratings collected over a range of temperatures showed that LTN increased monotonically on heat-sensitive sites but not on cold-sensitive sites. These results provide psychophysical evidence that stimulation from primary afferent fibers with thresholds in the range of warm fibers and cold fibers is relayed to the pain pathway. However, the labile nature of LTN implies that these lowthreshold nociceptive inputs are subject to inhibitory controls. The implications of these findings for the roles of putative temperature receptors and nociceptors in innocuous thermoreception and thermal pain are discussed.

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“…Furthermore, TRPA1 was shown to be a receptor for several pungent compounds, including the active ingredients in wasabi, cinnamon, and uncooked garlic [40,[102][103][104]. Several laboratories have examined the correlation between cold responses and these agonists, with mixed and inconclusive results [40,72,[102][103][104][105]. Thus, a chilly controversy arose regarding the involvement of TRPA1 in thermosensation, one that would presumably be resolved by the study of TRPA1-null mice.…”

Section: Mouse Models Deficient In Temperature Sensingmentioning

confidence: 99%

Temperature sensing across species

McKemy

2007

Pflugers Arch - Eur J Physiol

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The ability to detect changes in temperature is a fundamental sensory mechanism for every species and provides organisms with a detailed view of the environment. This review focuses on what is known of the neuronal and molecular substrates for thermosensation across species, focusing on the three robust model systems extensively used to study sensory signaling, the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the laboratory mouse. Nematodes migrate to thermal climes that are amenable to their survival, a behavior that is regulated primarily through a single sensory neuron. Additionally, nematodes "learn" to seek out this temperate zone based upon their prior experience, a robust model of learning and memory. Drosophila larvae also prefer select thermal zones that are optimal for growth and have also developed vigorous mechanisms to avoid unfavorable conditions. In mammals, the transduction mechanisms for thermosensation have been identified primarily due to the fact that naturally occurring plant products evoke distinct psychophysical sensation of temperature change. More remarkably, the elucidation of the molecular sensors in mammals, along with those in Drosophila, has demonstrated conservation in the molecular mediators of temperature sensation across diverse species.

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TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol

Cited by 225 publications

References 23 publications

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

Nociceptive sensations evoked from ‘spots’ in the skin by mild cooling and heating

Temperature sensing across species

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