• J Pain · May 2016

    Human Genetic Variability Contributes to Post-operative Morphine Consumption.

    • Manuela De Gregori, Luda Diatchenko, Pablo M Ingelmo, Valerio Napolioni, Pal Klepstad, Inna Belfer, Valeria Molinaro, Giulia Garbin, Guglielmina N Ranzani, Giovanni Alberio, Marco Normanno, Federica Lovisari, Marta Somaini, Stefano Govoni, Elisa Mura, Dario Bugada, Thekla Niebel, Michele Zorzetto, Simona De Gregori, Mariadelfina Molinaro, Guido Fanelli, and Massimo Allegri.
    • Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; SIMPAR (Study In Multidisciplinary Pain Research) Group, UO 2(a) Anestesia, Rianimazione e Terapia Antalgica, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; YAP (Young Against Pain) Group, UO 2(a) Anestesia, Rianimazione e Terapia Antalgica, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
    • J Pain. 2016 May 1; 17 (5): 628-36.

    UnlabelledHigh 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.PerspectiveThis 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.Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

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