Background　Recent studies demonstrate that the imbalance between acetylation and deacetylation of histone proteins correlates with abnormal transcription of nociceptive processing genes, strongly associated with the development of inflammatory or neuropathic pain. The treatment of histone acetyltransferase inhibitor(HATI) has been reported to alleviate pain by blocking the upregulation of chemokines and cyclooxygenase-2, and can be a drug target for the treatment of chronic pain.　Objective　To review the roles of histone acetylation in the development of chronic pain and the application of histone acetyl transferase inhibitors to the treatment of chronic pain.　Content　In inflammatory and neuropathic pain, over-acetylation of histone protein following the upregulation of histone acetyltransferase(HAT) is associated with pain symptoms. HATI attenuates hyperalgesia probably through inhibiting chemokines, cyclo-oxygenase-2 (COX-2) and cyclin-dependent kinase 5 (Cdk5). The available HATI include dual substrates inhibitor, derivatives of natural product(such as, garcinia), small molecule HAT inhibitors (C646), and inhibitors to bromodomain of HAT. Garcinia has limited water solubility and bioavailability and is difficult to penetrate blood brain barrier. C646, the only HATI with high potency and specificity, is proved to be highly effective to relive pain symptoms.　Trend　HATI have therapeutic potentials for the treatment of chronic pain. Further investigations are required to develop and validate more HATI.