Abstract: Chronic pain is a major factor leading to disability worldwide, and its mechanisms and treatment strategies have always faced significant challenges. In recent years, studies have found that calcitonin gene - related peptide (CGRP) is a key mediator in the regulation of chronic pain, and its expression level is precisely regulated by epigenetic mechanisms. Investigating the epigenetic regulation mechanism of CGRP is an effective way to find out its involvement in the occurrence and development of pain, which provides a new perspective for revealing the molecular mechanism of chronic pain. This review summarizes the research progress on the mechanisms of CGRP and its epigenetic findings in chronic pain, including DNA methylation, miRNA regulation, and histone modification, helping clinicians better understand the key role of CGRP in the pathophysiology of pain and providing new targets for pain treatment.