Cold sensitivity of recombinant TRPA1 channels

Sawada, Yosuke; Hosokawa, Hiroshi; Hori, Aiko; Matsumura, Kiyoshi; Kobayashi, Shígeo

doi:10.1016/j.brainres.2007.05.047

Cited by 163 publications

(147 citation statements)

References 24 publications

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“…Furthermore, no correlation was found between cold sensitivity and response to CM, a specific TRPA1 agonist. It should be pointed out that a recent study has found a strong correlation between sensitivity to TRPA1 agonists and sensitivity to deep cooling in mice DRG (Sawada et al, 2007). The possibility that cold responses in the nodose may be caused by a novel TRPA1-like channel with similar pharmacological properties to TRPA1 appears incompatible with the major reduction in cold sensitivity we observed in TRPA1(Ϫ/Ϫ) animals.…”

Section: Contribution Of Trpa1 To Cold Sensing At Visceral Neuronsmentioning

confidence: 54%

TRPA1 Channels Mediate Cold Temperature Sensing in Mammalian Vagal Sensory Neurons: Pharmacological and Genetic Evidence

Fajardo

Meseguer²,

Belmonte³

et al. 2008

J. Neurosci.

146

118

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Section: Contribution Of Trpa1 To Cold Sensing At Visceral Neuronsmentioning

confidence: 54%

TRPA1 Channels Mediate Cold Temperature Sensing in Mammalian Vagal Sensory Neurons: Pharmacological and Genetic Evidence

Fajardo

Meseguer²,

Belmonte³

et al. 2008

J. Neurosci.

146

118

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“…This is mainly because of the substantial overlap in stimuli that activate TRPM8 and TRPA1: both channels were shown to be activated by icilin, cold and menthol (McKemy et al, 2002;Peier et al, 2002a;Story et al, 2003;Karashima et al, 2007). It should be noted that whether TRPA1 plays a role as a cold sensor in vivo remains a matter of strong debate (Story et al, 2003;Jordt et al, 2004;Bautista et al, 2006;Kwan et al, 2006;Sawada et al, 2007;Zurborg et al, 2007). Previous studies have often used TRPA1-selective agonists such as MO to discriminate between TRPA1-and TRPM8-mediated responses.…”

Section: Discussionmentioning

confidence: 99%

Transient Receptor Potential Channels in Sensory Neurons Are Targets of the Antimycotic Agent Clotrimazole

Meseguer¹,

Karashima

Talavera

et al. 2008

J. Neurosci.

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Clotrimazole (CLT) is a widely used drug for the topical treatment of yeast infections of skin, vagina, and mouth. Common side effects of topical CLT application include irritation and burning pain of the skin and mucous membranes. Here, we provide evidence that transient receptor potential (TRP) channels in primary sensory neurons underlie these unwanted effects of CLT. We found that clinically relevant CLT concentrations activate heterologously expressed TRPV1 and TRPA1, two TRP channels that act as receptors of irritant chemical and/or thermal stimuli in nociceptive neurons. In line herewith, CLT stimulated a subset of capsaicin-sensitive and mustard oil-sensitive trigeminal neurons, and evoked nocifensive behavior and thermal hypersensitivity with intraplantar injection in mice. Notably, CLTinduced pain behavior was suppressed by the TRPV1-antagonist BCTC [(N-(-4-tertiarybutylphenyl)-4-(3-cholorpyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide)]and absent in TRPV1-deficient mice. In addition, CLT inhibited the cold and menthol receptor TRPM8, and blocked menthol-induced responses in capsaicin-and mustard oil-insensitive trigeminal neurons. The concentration for 50% inhibition (IC 50 ) of inward TRPM8 current was ϳ200 nM, making CLT the most potent known TRPM8 antagonist and a useful tool to discriminate between TRPM8-and TRPA1-mediated responses. Together, our results identify TRP channels in sensory neurons as molecular targets of CLT, and offer means to develop novel CLT preparations with fewer unwanted sensory side effects.

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“…Human genetic studies have suggested TRPA1 contributes to variation in cold-pain sensitivity (5). Although TRPA1 may respond to cold indirectly through cold-induced intracellular calcium release (10), slow temperature ramps can activate TRPA1 in excised patches in the absence of calcium (82,83). However, the contribution of TRPA1 to cold sensation is debated since TRPA1 activation was not observed in a heterologous expression system or cultured TG neurons to which relatively short cold stimuli to 5°C were applied (84), and not all Known or proposed transduction mechanisms in uninjured mammalian nociceptor peripheral terminals.…”

Section: Transduction Of Noxious Coldmentioning

confidence: 99%

Nociceptors: the sensors of the pain pathway

Dubin

Patapoutian²

2010

J. Clin. Invest.

1,014

856

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Specialized peripheral sensory neurons known as nociceptors alert us to potentially damaging stimuli at the skin by detecting extremes in temperature and pressure and injury-related chemicals, and transducing these stimuli into long-ranging electrical signals that are relayed to higher brain centers. The activation of functionally distinct cutaneous nociceptor populations and the processing of information they convey provide a rich diversity of pain qualities. Current work in this field is providing researchers with a more thorough understanding of nociceptor cell biology at molecular and systems levels and insight that will allow the targeted design of novel pain therapeutics.

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Cold sensitivity of recombinant TRPA1 channels

Cited by 163 publications

References 24 publications

TRPA1 Channels Mediate Cold Temperature Sensing in Mammalian Vagal Sensory Neurons: Pharmacological and Genetic Evidence

TRPA1 Channels Mediate Cold Temperature Sensing in Mammalian Vagal Sensory Neurons: Pharmacological and Genetic Evidence

Transient Receptor Potential Channels in Sensory Neurons Are Targets of the Antimycotic Agent Clotrimazole

Nociceptors: the sensors of the pain pathway

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