Abstract: More than 20% of adults worldwide suffer from different types of chronic pain, which are frequently associated with several comorbidities and adverse impact on patient quality of life. Although several approved analgesic drugs are commercially available, they are often hampered by severe side effects and/or insufficient efficacy. One of the most likely possibilities is to develop novel drugs from outcomes of studying the epigenetic mechanisms of chronic pain. A growing body of evidence has emerged in the field of pain epigenetics; however, the field is still very much in its infancy. Epigenetic mechanisms in mammals include DNA methylation, post-translational histone modification, chromatin remodeling and non-coding RNAs. One of the most popular and key epigenetic mechanisms in regulation of gene expression is methylation of cytosines.  In the past decade, our group has been focused on the roles of DNA methylation in the different kinds of chronic pain conditions. Our data strongly suggest that imbalance of DNA demethylation homeostasis contributes to the development of chronic pain hypersensitivity. Obviously, there are many challenging research issues that require to be well addressed to fill in the gaps in our knowledge related to the potential for drugging the pain epigenome.

Key words: Chronic pain, Epigenetic regulation, DNA methylation and demethylation Homeostasis