Role of CYP2D6 Polymorphisms in the Outcome of Postoperative Pain Treatment

Pain Med. 2015 Oct;16(10):2012-23. doi: 10.1111/pme.12778. Epub 2015 May 19.


Objective: To investigate the role of CYP2D6 phenotype in the outcome of postoperative (PO) pain (POP) treatment.

Design: Longitudinal cohort study. Open-label trial with post hoc analysis.

Setting: General Hospital Surgery and Recovery Units.

Patients: Ninety unrelated Caucasians submitted to abdominal/thoracic surgery.

Interventions: Standard multimodal POP treatment including opioids (tramadol) and nonsteroidal anti-inflammatory drugs (ketoprofen) at different dosages and infusion rates according to the predicted mild, moderate, or severe POP.

Outcome measures: Pain (Numeric Rating Scale-NRS) and sedation (Ramsay Sedation Scale-RSS) up to 24 hours after surgery. By genotyping 16 CYP2D6 alleles, the four CYP2D6 phenotypes poor metabolizer (PM), intermediate metabolizers (IM), extensive metabolizers (EM) and ultrarapid metabolizers (UM) were predicted.

Results: As compared with the CYP2D6-EM phenotype, in the early PO time (30 min) a higher RSS mean score in IM was observed (P = 0.035). A suggestion towards higher mean score in PM (P = 0.091) and a minor mean score in UM (P = 0.091) was also detected. No difference in the outcome of pain across the CYP2D6 phenotypes was observed.

Conclusions: In respect to the normal CYP2D6 phenotype, our results suggested that slowly metabolizers (IMs and PMs) might have a major sedation, whereas more rapid metabolizers (UM) a minor sedation, in the early time after surgery. A minor role of CYP2D6 phenotype in PO analgesia may be suggested.

Keywords: CYP2D6; Cytochrome P450; Ketoprofen; POP; Pharmacogenetics; Postoperative Pain Treatment; Tramadol.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics / therapeutic use*
  • Cytochrome P-450 CYP2D6 / genetics*
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Italy / epidemiology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Pain Measurement / statistics & numerical data
  • Pain, Postoperative / drug therapy*
  • Pain, Postoperative / epidemiology
  • Pain, Postoperative / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Treatment Outcome
  • Young Adult


  • Analgesics
  • Genetic Markers
  • Cytochrome P-450 CYP2D6