Epigenetics and the transition from acute to chronic pain.
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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.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.This is a focused literature review of epigenetic science and its relationship to chronic pain.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.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.
Published Version (Please cite this version)
Buchheit, Thomas, Thomas Van de Ven and Andrew Shaw (2012). Epigenetics and the transition from acute to chronic pain. Pain medicine (Malden, Mass.), 13(11). pp. 1474–1490. 10.1111/j.1526-4637.2012.01488.x Retrieved from https://hdl.handle.net/10161/19643.
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Dr. Buchheit serves as Director of the Regenerative Pain Therapies Program in the Duke Center for Translational Pain Medicine (CTPM), and practices Pain Medicine at both Duke University and the Durham VAMC. His research focus is on the local and systemic inflammatory mechanisms that drive pain in arthritis and nerve injury. He has led and participated in several multicenter research projects that have studied patients at Duke, the Durham VAMC, and Walter Reed National Military Medical Center, clarifying post-amputation pain phenotypes and mechanisms that drive the chronification of pain. These research pursuits have guided the clinical and translational programs of CTPM that strive develop biologically-based methods for the treatment of arthritis and degenerative musculoskeletal conditions. The program’s overarching goal is to move beyond opioids, steroids and anti-inflammatory medications for the treatment of pain.
Dr. Buchheit currently serves on the Editorial Board of Pain Medicine and recently completed service as Pain Medicine Division Chief in the Duke Department of Anesthesiology. He also serves on the Board of The Pain Society of the Carolinas and previously on the American Society of Anesthesiologists Pain Medicine Committee, (2012-2014), as an American Board of Anesthesiology Question Author (2011-2014), and President of Pain Society of the Carolinas (2015-2017).
Dr Shaw is an Associate Professor of Anesthesiology and Critical Care Medicine at Duke University Medical Center. He is a Fellow of the Royal College of Anaesthetists (UK) and a Fellow of the American College of Critical Care Medicine. He has practiced cardiothoracic anesthesiology and critical care medicine for more than 15 years in the UK and USA, has authored 3 textbooks and more than 100 original papers. He currently runs the iPEGASUS initiative, an international surgical outcomes consortium focused on genetics and genomics in perioperative medicine. His clinical practice is cardiothoracic anesthesia and surgical critical care medicine. His translational research interests include the use of metabolomics, proteomics and genomics for biomarker discovery in acute illness and injury; his clinical research interests include observational and interventional trials of candidate interventions to prevent and treat adverse outcomes following surgery. His research is funded by the National Institutes of Health, the US Department of Defence, private philanthropy and by industry.
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