A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice

Neuron. 1999 Sep;24(1):253-60. doi: 10.1016/s0896-6273(00)80837-5.


There is great interest in discovering new targets for pain therapy since current methods of analgesia are often only partially successful. Although protein kinase C (PKC) enhances nociceptor function, it is not known which PKC isozymes contribute. Here, we show that epinephrine-induced mechanical and thermal hyperalgesia and acetic acid-associated hyperalgesia are markedly attenuated in PKCepsilon mutant mice, but baseline nociceptive thresholds are normal. Moreover, epinephrine-, carrageenan-, and nerve growth factor- (NGF-) induced hyperalgesia in normal rats, and epinephrine-induced enhancement of tetrodotoxin-resistant Na+ current (TTX-R I(Na)) in cultured rat dorsal root ganglion (DRG) neurons, are inhibited by a PKCepsilon-selective inhibitor peptide. Our findings indicate that PKCepsilon regulates nociceptor function and suggest that PKCepsilon inhibitors could prove useful in the treatment of pain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetic Acid
  • Analgesia
  • Analgesics
  • Animals
  • Carrageenan
  • Enzyme Inhibitors
  • Epinephrine
  • Hot Temperature
  • Hyperalgesia / etiology
  • Hyperalgesia / genetics
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism*
  • Mice
  • Mutation*
  • Nerve Growth Factor
  • Nociceptors / physiology*
  • Protein Kinase C / genetics*
  • Protein Kinase C / metabolism*
  • Rats
  • Signal Transduction*
  • Sodium Channels / drug effects
  • Sodium Channels / physiology
  • Tetrodotoxin / pharmacology


  • Analgesics
  • Enzyme Inhibitors
  • Isoenzymes
  • Sodium Channels
  • Tetrodotoxin
  • Carrageenan
  • Nerve Growth Factor
  • Protein Kinase C
  • Acetic Acid
  • Epinephrine