Human Genetic Variability Contributes to Postoperative Morphine Consumption.

J Pain

SIMPAR (Study In Multidisciplinary Pain Research) Group, UO 2(a) Anestesia, Rianimazione e Terapia Antalgica, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Anesthesia, Critical Care and Pain Medicine, Department of Surgical Sciences, University of Parma, Parma, Italy; UO 2(a) Anestesia, Rianimazione e Terapia Antalgica, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. Electronic address:

Published: May 2016

AI Article Synopsis

  • The study investigates how genetic and environmental factors contribute to differences in opioid consumption after surgery, focusing on single nucleotide polymorphisms (SNPs) in specific genes.
  • An analysis of 20 SNPs from 201 patients showed that certain combinations of SNPs in the OPRM1, COMT, and ESR1 genes significantly affect morphine consumption and pain levels.
  • Results indicate that using a combination of genetic markers could improve understanding of opioid needs and lead to better diagnostic tools for managing pain post-surgery.

Article Abstract

Unlabelled: High interindividual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain, and single nucleotide polymorphisms (SNPs) within opioid receptor μ 1 (OPRM1), catechol-O-methyltransferase (COMT), uridine diphosphate glucose-glucuronosyltransferase-2B7, and estrogen receptor (ESR1) gene loci to elucidate genetic prediction of opioid consumption. We analyzed 20 SNPs in 201 unrelated Caucasian patients who underwent abdominal surgery and who were receiving postoperative patient-controlled analgesia-administered morphine. Morphine consumption and pain intensity were dependent variables; age and sex were covariates. A haplotype of 7 SNPs in OPRM1 showed significant additive effects on opioid consumption (P = .007); a linear regression model including age and 9 SNPs in ESR1, OPRM1, and COMT explained the highest proportion of variance of morphine consumption (10.7%; P = .001). The minimal model including 3 SNPs in ESR1, OPRM1, and COMT explained 5% of variance (P = .007). We found a significant interaction between rs4680 in COMT and rs4986936 in ESR1 (P = .007) on opioid consumption. SNPs rs677830 and rs540825 of OPRM1 and rs9340799 of ESR1 were nominally associated with pain Numeric Rating Scale scores. Combinations of genetic variants within OPRM1, COMT, and ESR1 better explain variability in morphine consumption than single genetic variants. Our results contribute to the development of genetic markers and statistical models for future diagnostic tools for opioid consumption/efficacy.

Perspective: This article presents the efforts dedicated to detect correlations between the genetic polymorphisms and the clinical morphine effect self-administered by patients using a patient-controlled analgesia pump after major surgery. The clinical effect is expressed in terms of morphine consumption and pain scores. REGISTERED ON CLINICALTRIALS.GOV: NCT01233752.

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Source
http://dx.doi.org/10.1016/j.jpain.2016.02.003DOI Listing

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