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 (ΔNRS ≥ 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.

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Keywords Cardiac surgery, COMTVal158Met polymorphism, Genetics, Intensive care patients, Numerical rating scale, Pain sensitivity
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Journal British Journal of Clinical Pharmacology
Ahlers, S.J.G.M, Elens, L, van Gulik, L, van Schaik, R.H.N, van Dongen, E.H.P.A, Bruins, P, … Knibbe, C.A.J. (2013). The Val158Met polymorphism of the COMT gene is associated with increased pain sensitivity in morphine-treated patients undergoing a painful procedure after cardiac surgery. British Journal of Clinical Pharmacology, 75(6), 1506–1515. doi:10.1111/bcp.12052