Inflammatory-linked changes in CpG island methylation of three opioid peptide genes in a rat model for pain

PLoS One. 2018 Jan 19;13(1):e0191698. doi: 10.1371/journal.pone.0191698. eCollection 2018.


Expression of the opioid peptide genes proopiomelanocortin (Pomc), proenkephalin (Penk), and prodynorphin (Pdyn), in immune cells plays a key role in endogenous pain control. In a rat model of painful unilateral paw inflammation, we isolated cells from popliteal lymph nodes and evaluated the role of CpG island C5-methylation on the transcriptional activation of those genes. Using methylated DNA immunoprecipitation, we sorted gDNA into methylated (me) and non-me fractions and then determined the CpG island methylation status of each fraction via quantitative Real Time-PCR (qRT-PCR). In silico analysis by MethPrimer software identified one CpG island in Pdyn and three each in Pomc and Penk. No substantial changes in C5-methylation of any gene were observed. In conclusion, the CpG island methylation status does not seem to be a key regulator of opioid gene activation in immune cells during peripheral tissue inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CpG Islands*
  • DNA Methylation*
  • Disease Models, Animal
  • Enkephalins / genetics*
  • Gene Expression Regulation
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Male
  • Pain / genetics*
  • Pain / metabolism
  • Pro-Opiomelanocortin / genetics*
  • Protein Precursors / genetics*
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction


  • Enkephalins
  • Protein Precursors
  • proenkephalin
  • Pro-Opiomelanocortin
  • preproenkephalin

Grant support

This work was supported by the Bundesministerium für Bildung und Forschung (; grant number 01EC1403E/F). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.