The V al158 M et polymorphism of the COMT gene is associated with increased pain sensitivity in morphine‐treated patients undergoing a painful procedure after cardiac surgery

• Published in: British journal of clinical pharmacology Vol. 75; no. 6; pp. 1506 - 1515
• Main Authors: Ahlers, Sabine J. G. M., Elens, Laure L., van Gulik, Laura, van Schaik, Ron H., van Dongen, Eric P. A., Bruins, Peter, Tibboel, Dick, Knibbe, Catherijne A. J.
• Format: Journal Article
• Language: English
• Published: 01-06-2013
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12052

Aims
The catechol‐
O
‐methyltransferase (
COMT
)
V
al158
M
et 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
COMT

V
al158
M
et 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
COMT

V
al158
M
et polymorphism. All patients were treated with continuous morphine infusions for pain at rest, and received a bolus of morphine (2.5 or 7.5 mg) 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
M
et‐variant allele. During the painful procedure, the mean
NRS
score was significantly higher for
M
et/
M
et patients compared with
V
al/
M
et and
V
al/
V
al patients (mean
NRS
3.4 ± 2.8, 2.7 ± 2.4 and 1.7 ± 1.7, respectively;
P
= 0.04). In
M
et/
M
et patients, the increase in
NRS
scores during the painful procedure compared with the baseline
NRS
score was clinically relevant (Δ
NRS
≥ 1.3) and statistically significant and appeared to be independent of sex and the morphine bolus dose.
Conclusions
Our results show that the
COMT

V
al158
M
et 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.