Abstract
About 25 million American adults experience pain daily and one of the most commonly prescribed drugs to treat pain are opioids. Prolonged opioid usage and dose escalations can cause a paradoxical response where patients experience enhanced pain sensitivity. This opioid induced hyperalgesia (OIH) is a major hurdle when treating pain in the clinic because its underlying mechanisms are still not fully understood. OIH is also commonly overlooked and lacks guidelines to prevent its onset. Research on pain disorders and opioid usage have recognized potential epigenetic drivers of disease including DNA methylation, histone modifications, miRNA regulation, but their involvement in OIH has not been well studied. This article discusses epigenetic changes that may contribute to pathogenesis, with an emphasis on miRNA alterations in OIH. There is a crucial gap in knowledge including how multiple epigenetic modulators contribute to OIH. Elucidating the epigenetic changes underlying OIH and the crosstalk among these mechanisms could lead to the development of novel targets for the prevention and treatment of this painful phenomena.