Transcription-independent expression of PKMζ in the anterior cingulate cortex contributes to chronically maintained neuropathic pain

Mol Pain. 2018 Jan-Dec:14:1744806918783943. doi: 10.1177/1744806918783943.


Protein kinase M ζ is well known for its role in maintaining memory and pain. Previously, we revealed that the activation of protein kinase M ζ in the anterior cingulate cortex plays a role in sustaining neuropathic pain. However, the mechanism by which protein kinase M ζ is expressed in the anterior cingulate cortex by peripheral nerve injury, and whether blocking of protein kinase M ζ using its inhibitor, zeta inhibitory peptide, produces analgesic effects in neuropathic pain maintained chronically after injury, have not previously been resolved. In this study, we show that protein kinase M ζ expression in the anterior cingulate cortex is enhanced by peripheral nerve injury in a transcription-independent manner. We also reveal that the inhibition of protein kinase M ζ through zeta inhibitory peptide treatment is enough to reduce mechanical allodynia responses in mice with one-month-old nerve injuries. However, the zeta inhibitory peptide treatment was only effective for a limited time.

Keywords: Protein kinase M ζ; anterior cingulate cortex; chronic pain; neuropathic pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell-Penetrating Peptides
  • Chronic Pain / enzymology*
  • Chronic Pain / genetics*
  • Chronic Pain / pathology
  • Gyrus Cinguli / enzymology*
  • Gyrus Cinguli / pathology
  • Lipopeptides / pharmacology
  • Long-Term Potentiation
  • Male
  • Mice, Inbred C57BL
  • Neuralgia / enzymology*
  • Neuralgia / genetics*
  • Neuralgia / pathology
  • Peripheral Nerves / pathology
  • Protein Kinase C / metabolism*
  • Receptors, AMPA
  • Synapses / metabolism
  • Transcription, Genetic* / drug effects


  • Cell-Penetrating Peptides
  • Lipopeptides
  • Receptors, AMPA
  • zeta-inhibitory peptide
  • Protein Kinase C
  • glutamate receptor ionotropic, AMPA 2