The menthol receptor TRPM8 is the principal detector of environmental cold

@article{Bautista2007TheMR,
  title={The menthol receptor TRPM8 is the principal detector of environmental cold},
  author={Diana M. Bautista and Jan Siemens and Joshua M. Glazer and Pamela R. Tsuruda and Allan I. Basbaum and Cheryl L. Stucky and Sven-Eric Jordt and David Julius},
  journal={Nature},
  year={2007},
  volume={448},
  pages={204-208}
}
Sensory nerve fibres can detect changes in temperature over a remarkably wide range, a process that has been proposed to involve direct activation of thermosensitive excitatory transient receptor potential (TRP) ion channels. One such channel—TRP melastatin 8 (TRPM8) or cold and menthol receptor 1 (CMR1)—is activated by chemical cooling agents (such as menthol) or when ambient temperatures drop below ∼26 °C, suggesting that it mediates the detection of cold thermal stimuli by primary afferent… 
The Role of Cold-Sensitive Ion Channels in Peripheral Thermosensation
TLDR
This mini-review gives a brief overview of the way by which ion channels contribute to cold sensation, discusses the controversy around the cold-sensitivity of TRPA1, and provides an assessment of some recently-proposed novel cold-transduction mechanisms.
Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms
  • A. Babes
  • Chemistry, Medicine
    Biophysical Reviews
  • 2009
TLDR
Evidence supporting a role for each of the TRP channels in cold transduction is reviewed, focusing on their biophysical properties, expression pattern, and modulation by pro-inflammatory mediators.
The TRPM2 ion channel is required for sensitivity to warmth
TLDR
Cal calcium imaging is used to identify a population of thermally sensitive somatosensory neurons which do not express any of the known thermally activated TRP channels, and it is shown that the ion channel generating heat sensitivity in these neurons is TRPM2.
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TLDR
PBMC is an attractive compound that serves as a template for the formulation of highly specific and potent TRPM8 antagonists that will have utility both in vitro and in vivo, and is ineffective against oxaliplatin-induced neuropathic cold hypersensitivity.
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In the somatosensory system, cold thermoreceptor neurons and cold nociceptors are responsible for the detection of environmental low temperatures. The underlying machinery is far from simple; it is a
Negative Modulation of TRPM8 Channel Function by Protein Kinase C in Trigeminal Cold Thermoreceptor Neurons
TLDR
Biophysical analysis indicated that PKC-dependent downregulation of TRPM8 is mainly due to a decreased maximal conductance value, and complementary noise analysis revealed a reduced number of functional channels at the cell surface, providing important clues to understanding the molecular mechanisms of how PKC activity modulates TR PM8 channels in CTNs.
Therapeutic Potential of TRPM 8 Modulators
The perception of temperature is a key tenet of sensory physiology and is critical in not only acute responses to changes in our environment, but also fundamental in regulating homeostatic mechanisms
TRPM3 Is a Nociceptor Channel Involved in the Detection of Noxious Heat
TLDR
Evidence is provided that TRPM3 functions as a chemo- and thermosensor in the somatosensory system and an unanticipated role for TR PM3 as a thermosensitive nociceptor channel implicated in the detection of noxious heat is revealed.
Epidermal expression of human TRPM8, but not of TRPA1 ion channels, is associated with sensory responses to local skin cooling.
TLDR
The present observations demonstrating a lack of association of TRPA1 channel expression with cold sensitivity related measures reinforce doubts about involvement of this channel in cold pain in humans.
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