Explorative Study About the Degree of DNA Methylation Related to Acute Perioperative Pain Treatment
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- DNA Methylation
研究概览
简要总结
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.
The primary objective of this study is to assess the degree of perioperative DNA methylation (extracted from whole blood) in patients undergoing major surgery exposed to opioids according to current clinical practice compared to preoperative baseline levels. The timing (preoperative vs intraoperative vs postoperative) in which the possible increase of the degree of DNA methylation will happen wil be assessed.
20 consecutive patients undergoing major surgery performed under general anesthesia that have expressed their consent to participate to the study will be enrolled. This sample is adequate to allow the observation of a possible increase of DNA methylation in opioid-naive patients exposed to anesthesia/analgesia based on opiates according to current clinical practice.
详细描述
During perioperative period surgical patients experience profound changes in their physiological processes. In addition to surgical stress, these variations are in part due to pharmacological treatments commonly used for anesthesia and analgesia during and after surgical procedure.
Opioids are essential drugs for the management of acute perioperative pain. 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.
Epigenetic alterations typically involve changes in chromatin structure, which is composed of DNA, histones and non-histone proteins. Main changes in clinical setting are covalent modifications of N-terminal sequences of histone proteins and DNA methylation. In particular, DNA methylation is carried out with the addition of a methyl group on the fifth carbon atom of cytosine residues (5mC), mainly localized in CpG regions.
DNA methylation is considered as a mechanism of gene silencing. It is a complex process regulated by a whole family of enzymes called DNA methyl-transferase (DNMTs: DNMT1, DNMT2, DNMT3a, DNMT3B, and DNMT3L) that catalyze the transfer of a methyl group.
In particular DNMT 1, 3a, 3b were studied during the development of a neuropathic pain model. Through immunohistochemical analysis it was observed that in the dorsal root ganglion of an adult rat (L4-5) DNMT3B showed an important up-regulation that is observed already 1 week after the induction of the model and that persists for 4 weeks; on the contrary, DNMT1 and DNMT3a showed a moderate and transient up-regulation. Other studies have shown that in a different pattern of pain, acute inflammatory, the expression levels of DNMT3a and DNMT3B are particularly high.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •renal and hepatic failure; OSAS; Apfel score > 3.
结局指标
主要结局
DNA Methylation
时间窗: 2 days
次要结局
未报告次要终点
研究者
Andrea Fanelli
MD
University of Bologna