Pathological pain refers to the pain that caused by the tissue injury due to trauma, infection, tumor, etc. It may turn into chronic pain if it lasts for more than one month or remains when the tissue injury is healed. Patients with chronic pain often suffer insomnia, anxiety, depression and other mental disorders, which may seriously impair their physical function and quality of life, subsequently leading to many social and economic problems. Recent studies have found that epigenetic regulation may explain, at molecular level, the pathogenesis of pathological pain, including inflammation pain, neuropathic pain and psychological pain, which may lead to the development of its therapeutic means. In this article, we reviewed the latest research progress of epigenetic regulation of chronic pathological pain, including DNA methylation, histone acetylation and miRNA activity.