The Val158Met polymorphism of the COMT gene is associated with increased pain sensitivity in morphine-treated patients undergoing a painful procedure after cardiac surgery

被引:44
作者
Ahlers, Sabine J. G. M. [1 ,2 ,3 ]
Elens, Laure L. [4 ]
van Gulik, Laura [5 ]
van Schaik, Ron H. [4 ]
van Dongen, Eric P. A. [5 ]
Bruins, Peter [5 ]
Tibboel, Dick [2 ,3 ]
Knibbe, Catherijne A. J. [1 ,2 ,3 ,6 ]
机构
[1] St Antonius Hosp, Dept Clin Pharm, NL-3440 EM Nieuwegein, Netherlands
[2] Sophia Childrens Univ Hosp, Erasmus Med Ctr, NL-3015 GJ Rotterdam, Netherlands
[3] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Pediat Surg, NL-3015 GJ Rotterdam, Netherlands
[4] Erasmus Univ, Med Ctr, Dept Clin Chem, NL-3015 CE Rotterdam, Netherlands
[5] St Antonius Hosp, Dept Anaesthesiol Intens Care & Pain Management, NL-3440 EM Nieuwegein, Netherlands
[6] Leiden Amsterdam Ctr Drug Res, Div Pharmacol, NL-2333 CC Leiden, Netherlands
关键词
cardiac surgery; COMTVal158Met polymorphism; genetics; intensive care patients; numerical rating scale; pain sensitivity; POSTOPERATIVE PAIN; CANCER PAIN; VARIABILITY; PREDICTORS; PERCEPTION; ANALGESIA; RESPONSES;
D O I
10.1111/bcp.12052
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims The catechol-O-methyltransferase (COMT) Val158Met polymorphism affected pain sensitivity of healthy volunteers upon application of experimental pain stimuli. The relevance of these findings in morphine-treated postoperative cardiac patients undergoing painful healthcare procedures is unknown; therefore, the aim of this study was to investigate whether the COMTVal158Met polymorphism increases pain sensitivity in morphine-treated patients undergoing an unavoidable painful routine procedure after cardiac surgery. Methods One hundred and seventeen postoperative cardiac patients in the intensive care unit were genotyped for the COMTVal158Met polymorphism. All patients were treated with continuous morphine infusions for pain at rest, and received a bolus of morphine (2.5 or 7.5mg) before a painful procedure (turning and/or chest drain removal) on the first postoperative day. Numerical rating scale (NRS) scores were evaluated at the following four time points: at baseline (at rest), and before, during and after the painful procedure. Results Overall mean NRS scores were significantly higher in patients carrying the Met-variant allele. During the painful procedure, the mean NRS score was significantly higher for Met/Met patients compared with Val/Met and Val/Val patients (mean NRS 3.4 +/- 2.8, 2.7 +/- 2.4 and 1.7 +/- 1.7, respectively; P = 0.04). In Met/Met patients, the increase in NRS scores during the painful procedure compared with the baseline NRS score was clinically relevant (NRS 1.3) and statistically significant and appeared to be independent of sex and the morphine bolus dose. Conclusions Our results show that the COMTVal158Met polymorphism contributes to variability in pain sensitivity after cardiac surgery of morphine-treated patients in the intensive care unit, because Met-allele carriers were more sensitive to overall pain and procedure-related pain.
引用
收藏
页码:1506 / 1515
页数:10
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