Epigenetics and the Transition from Acute to Chronic Pain

OBJECTIVE: The objective of this study was to review the epigenetic modifications involved in the transition from acute to chronic pain and to identify potential targets for the development of novel, individualized pain therapeutics. BACKGROUND: Epigenetics is the study of heritable modifications in gene expression and phenotype that do not require a change in genetic sequence to manifest their effects. Environmental toxins, medications, diet, and psychological stresses can alter epigenetic processes such as DNA methylation, histone acetylation, and RNA interference. As epigenetic modifications potentially play an important role in inflammatory cytokine metabolism, steroid responsiveness, and opioid sensitivity, they are likely key factors in the development of chronic pain. Although our knowledge of the human genetic code and disease-associated polymorphisms has grown significantly in the past decade, we have not yet been able to elucidate the mechanisms that lead to the development of persistent pain after nerve injury or surgery. DESIGN: This is a focused literature review of epigenetic science and its relationship to chronic pain. RESULTS: Significant laboratory and clinical data support the notion that epigenetic modifications are affected by the environment and lead to differential gene expression. Similar to mechanisms involved in the development of cancer, neurodegenerative disease, and inflammatory disorders, the literature endorses an important potential role for epigenetics in chronic pain. CONCLUSIONS: Epigenetic analysis may identify mechanisms critical to the development of chronic pain after injury, and may provide new pathways and target mechanisms for future drug development and individualized medicine.