Specific involvement of PKC-epsilon in sensitization of the neuronal response to painful heat

Neuron. 1999 Jul;23(3):617-24. doi: 10.1016/s0896-6273(00)80813-2.


Pain is unique among sensations in that the perceived intensity increases, or sensitizes, during exposure to a strong stimulus. One important mediator of sensitization is bradykinin (BK), a peptide released as a consequence of tissue damage. BK enhances the membrane ionic current activated by heat in nociceptive neurons, using a pathway that involves activation of protein kinase C (PKC). We find that five PKC isoforms are present in sensory neurons but that only PKC-epsilon is translocated to the cell membrane by BK. The heat response is sensitized when constitutively active PKC-epsilon is incorporated into nociceptive neurons. Conversely, BK-induced sensitization is suppressed by a specific peptide inhibitor of PKC-epsilon. We conclude that PKC-epsilon is principally responsible for sensitization of the heat response in nociceptors by bradykinin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biological Transport / drug effects
  • Bradykinin / pharmacology
  • Carcinogens / pharmacology
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Ganglia, Spinal / cytology
  • Hot Temperature
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism*
  • Neurons, Afferent / cytology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / enzymology*
  • Nociceptors / drug effects
  • Nociceptors / physiology
  • Pain / metabolism*
  • Patch-Clamp Techniques
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Protein Kinase C-epsilon
  • Rats
  • Stimulation, Chemical
  • Tetradecanoylphorbol Acetate / pharmacology


  • Carcinogens
  • Isoenzymes
  • Prkce protein, rat
  • Protein Kinase C
  • Protein Kinase C-epsilon
  • Tetradecanoylphorbol Acetate
  • Bradykinin