To investigate the relationship between the downregulation of DNMT3a expression in the mPFC induced by PTX and chemotherapy‐related pain and negative emotions, we aimed to determine whether restoring DNMT3a levels in the mPFC could alleviate pain hypersensitivity, as well as anxiety‐like and depression‐like behaviors in PTX‐treated mice. The gene discussed is DNMT3A; the disease is depressive disorder.