Two populations of cold-sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor

Eur J Neurosci. 2004 Nov;20(9):2276-82. doi: 10.1111/j.1460-9568.2004.03695.x.


Cold sensing in mammals is not completely understood, although significant progress has been made recently with the cloning of two cold-activated ion channels, TRPM8 and TRPA1. We have used rat DRG neurons in primary culture and calcium fluorimetry to identify distinct populations of cold-sensitive neurons, which may underlie different functions. Menthol sensitivity clearly separated two classes of cold-responding neurons. One group was menthol-sensitive (MS), was activated at warmer temperatures and responded faster and with a larger increase in intracellular calcium concentration during cooling; the fraction of MS neurons in culture and their cold sensitivity were both increased in the presence of nerve growth factor. Neurons in the menthol-insensitive (MI) group required stronger cooling for activation than MS cells and neither their proportion nor their cold sensitivity were significantly altered by nerve growth factor. The two groups of cold-sensitive neurons also had different pharmacology. A larger fraction of MS cells were capsaicin-sensitive and coexpression of menthol and capsaicin sensitivity was observed in the absence of NGF. MI neurons were not stimulated by the super-cooling agent icilin or by the irritant mustard oil. Taken together these findings support a picture in which TRPM8 is the major player in detecting gentle cooling, while TRPA1 does not seem to be involved in cold sensing by MI neurons, at least in the temperature range between 32 and 12 degrees C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankyrins
  • Calcium / metabolism
  • Calcium Channels / deficiency
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / genetics
  • Capsaicin / pharmacology
  • Cells, Cultured
  • Cold Temperature*
  • Drug Synergism
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Ion Channels / drug effects
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Menthol / pharmacology
  • Mustard Plant
  • Neoplasm Proteins / drug effects
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nerve Growth Factor / metabolism*
  • Nerve Growth Factor / pharmacology
  • Neurons, Afferent / classification
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism*
  • Plant Extracts / pharmacology
  • Plant Oils
  • Pyrimidinones / pharmacology
  • Rats
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TRPM Cation Channels
  • Thermosensing / genetics*
  • Transient Receptor Potential Channels


  • Ankyrins
  • Calcium Channels
  • Ion Channels
  • Neoplasm Proteins
  • Plant Extracts
  • Plant Oils
  • Pyrimidinones
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • TRPM Cation Channels
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • Trpa1 protein, rat
  • Trpm8 protein, rat
  • Menthol
  • Nerve Growth Factor
  • icilin
  • Capsaicin
  • Calcium
  • mustard oil