Acute pain is associated with tissue damage, which results in the release of inflammatory mediators. Recent studies point to the involvement of epigenetic mechanisms (DNA methylation) in the development of pain. We have found that during acute inflammatory pain induced by the application of 10% mustard oil on the tongues of rats, levels of DNMT3a and 3b were elevated markedly (36 and 42 % respectively), whereas the level of DNMT1 was not changed significantly. Previous injection of Xefocam with 0,4 mg/kg dose decreased levels of DNMT3a and 3b (25 and 24% respectively). The level of DNMT1 was not changed significantly compared to the control group. The findings support the idea that inhibitors of DNA-methyltransferases could be useful for pain management. Our data suggest that NSAIDs (alone or in combination with DNMT inhibitors) may be proposed as possible epigenetic regulatory agents, which may play a role in epigenetic mechanisms indirectly through altering the activity of inflammatory mediators involved in pain development.