More than cool: promiscuous relationships of menthol and other sensory compounds

Mol Cell Neurosci. 2006 Aug;32(4):335-43. doi: 10.1016/j.mcn.2006.05.005. Epub 2006 Jul 7.


Several temperature-activated transient receptor potential (thermoTRP) ion channels are the molecular receptors of natural compounds that evoke thermal and pain sensations. Menthol, popularly known for its cooling effect, activates TRPM8--a cold-activated thermoTRP ion channel. However, human physiological studies demonstrate a paradoxical role of menthol in modulation of warm sensation, and here, we show that menthol also activates heat-activated TRPV3. We further show that menthol inhibits TRPA1, potentially explaining the use of menthol as an analgesic. Similar to menthol, both camphor and cinnamaldehyde (initially reported to be specific activators of TRPV3 and TRPA1, respectively) also modulate other thermoTRPs. Therefore, we find that many "sensory compounds" presumed to be specific have a promiscuous relationship with thermoTRPs.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Antipruritics / pharmacology*
  • Calcium / metabolism
  • Camphor / pharmacology
  • Capsaicin / pharmacology
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • Diagnostic Imaging / methods
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Ganglia, Spinal / cytology
  • Keratinocytes
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Menthol / pharmacology*
  • Mice
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology*
  • Patch-Clamp Techniques / methods
  • Rats
  • Temperature*
  • Transfection / methods
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / physiology


  • Antipruritics
  • Transient Receptor Potential Channels
  • Menthol
  • Camphor
  • Capsaicin
  • Calcium