In the last few years much attention has been paid to hyperalgesia induced by opioids, which represents a clinically significant condition following acute and chronic exposure to opioids. It has been suggested that the increase in gene expression of μ-opioid receptors and the development of hyperalgesia could be linked to epigenetic mechanisms. In particular the use of opioids seems to be related to an increase of the degree of DNA methylation. In the literature are not currently available data about the degree of DNA methylation in surgical patients, opioid-naive prior to surgery, receiving acute opioids treatment in the perioperative period.