Pharmacoepigenetics of the role of DNA methylation in μ-opioid receptor expression in different human brain regions

Epigenomics. 2016 Dec;8(12):1583-1599. doi: 10.2217/epi-2016-0072. Epub 2016 Sep 29.


Aim: Exposure to opioids has been associated with epigenetic effects. Studies in rodents suggested a role of varying degrees of DNA methylation in the differential regulation of μ-opioid receptor expression across the brain.

Methods: In a translational investigation, using tissue acquired postmortem from 21 brain regions of former opiate addicts, representing a human cohort with chronic opioid exposure, μ-opioid receptor expression was analyzed at the level of DNA methylation, mRNA and protein.

Results & conclusion: While high or low μ-opioid receptor expression significantly correlated with local OPRM1 mRNA levels, there was no corresponding association with OPRM1 methylation status. Additional experiments in human cell lines showed that changes in DNA methylation associated with changes in μ-opioid expression were an order of magnitude greater than differences in brain. Hence, different degrees of DNA methylation associated with chronic opioid exposure are unlikely to exert a major role in the region-specificity of μ-opioid receptor expression in the human brain.

Keywords: DNA methylation; OPRM1 methylation; human brain; μ-opioid receptor regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / toxicity*
  • Brain / drug effects*
  • Brain / metabolism
  • Cell Line, Tumor
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Middle Aged
  • Pain / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Opioid, mu / genetics*
  • Receptors, Opioid, mu / metabolism
  • Substance-Related Disorders / genetics*
  • Substance-Related Disorders / metabolism
  • Young Adult


  • Analgesics, Opioid
  • OPRM1 protein, human
  • RNA, Messenger
  • Receptors, Opioid, mu