Although PTX does not cross the blood‐brain barrier (BBB), it could stimulate an increased release of cytokines that readily penetrate the BBB and induce rapid structural and functional changes in the brain.[30] While prior research has highlighted the significant roles of DNMT3a and DNMT1 in regulating anxiety‐like behavior in the mPFC,[17, 31] our study emphasizes the specific contributions of DNA hypomethylation and reduced DNMT3a expression in pyramidal neurons to PTX‐induced pain hypersensitivity and anxiety. This evidence concerns the gene DNMT1 and Anxiety.