TRPM8 Axonal expression is decreased in painful human teeth with irreversible pulpitis and cold hyperalgesia

J Endod. 2007 Oct;33(10):1167-71. doi: 10.1016/j.joen.2007.06.018. Epub 2007 Aug 16.


Pulpitis pain might be triggered by a cold stimulus, yet the cellular mechanisms responsible for this phenomenon are largely unknown. One possible mechanism involves the direct activation of cold-responsive thermoreceptors. The purpose of this study was to evaluate the possible role of the TRPM8 thermoreceptor in cold-mediated noxious pulpal pain mechanisms by comparing expression patterns in pulpal nerves from healthy control molars to cold-sensitive painful molars with irreversible pulpitis. Samples were identically processed with the indirect immunofluorescence method, and images were obtained with confocal microscopy. The immunofluorescence intensity and area occupied by TRPM8 within N52/PGP9.5-identified nerve fibers were quantified. Results showed that relative to normal samples, TRPM8 nerve area expression was significantly less in the cold-sensitive painful samples (34.9% vs 8%, P <0.03), but with no significant difference in immunofluorescence intensity between the 2 groups. These results suggest that TRPM8 is most likely not involved in cold-mediated noxious pulpal pain mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axons / pathology*
  • Cold Temperature / adverse effects*
  • Dental Pulp / innervation*
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Hyperalgesia / pathology*
  • Microscopy, Confocal
  • Nerve Fibers / pathology
  • Nerve Fibers, Myelinated / pathology
  • Neurofilament Proteins / analysis
  • Nociceptors / pathology
  • Pain / pathology*
  • Pulpitis / pathology*
  • TRPM Cation Channels / analysis*
  • Thermoreceptors / pathology*
  • Ubiquitin Thiolesterase / analysis


  • Neurofilament Proteins
  • TRPM Cation Channels
  • TRPM8 protein, human
  • UCHL1 protein, human
  • neurofilament protein H
  • Ubiquitin Thiolesterase