Human Genetic Variability Contributes to Postoperative 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 MolinaroGuido Fanelli, Massimo Allegri

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)628-636
Number of pages9
JournalJournal of Pain
Volume17
Issue number5
DOIs
Publication statusPublished - May 1 2016

Fingerprint

Medical Genetics
Morphine
Catechol O-Methyltransferase
Single Nucleotide Polymorphism
Opioid Analgesics
Patient-Controlled Analgesia
Pain
Linear Models
Uridine Diphosphate Glucose
Glucuronosyltransferase
Genetic Models
Opioid Receptors
Statistical Models
Genetic Polymorphisms
Postoperative Pain
Genetic Markers
Estrogen Receptors
Haplotypes
Genes

Keywords

  • Acute postoperative pain
  • genetic variability
  • genetic variants combination
  • OPRM1 haplotype
  • postoperative opioid consumption

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology

Cite this

De Gregori, M., Diatchenko, L., Ingelmo, P. M., Napolioni, V., Klepstad, P., Belfer, I., ... Allegri, M. (2016). Human Genetic Variability Contributes to Postoperative Morphine Consumption. Journal of Pain, 17(5), 628-636. https://doi.org/10.1016/j.jpain.2016.02.003

Human Genetic Variability Contributes to Postoperative Morphine Consumption. / De Gregori, Manuela; Diatchenko, Luda; Ingelmo, Pablo M.; Napolioni, Valerio; Klepstad, Pal; Belfer, Inna; Molinaro, Valeria; Garbin, Giulia; Ranzani, Guglielmina N.; Alberio, Giovanni; Normanno, Marco; Lovisari, Federica; Somaini, Marta; Govoni, Stefano; Mura, Elisa; Bugada, Dario; Niebel, Thekla; Zorzetto, Michele; De Gregori, Simona; Molinaro, Mariadelfina; Fanelli, Guido; Allegri, Massimo.

In: Journal of Pain, Vol. 17, No. 5, 01.05.2016, p. 628-636.

Research output: Contribution to journalArticle

De Gregori, M, Diatchenko, L, Ingelmo, PM, Napolioni, V, Klepstad, P, Belfer, I, Molinaro, V, Garbin, G, Ranzani, GN, Alberio, G, Normanno, M, Lovisari, F, Somaini, M, Govoni, S, Mura, E, Bugada, D, Niebel, T, Zorzetto, M, De Gregori, S, Molinaro, M, Fanelli, G & Allegri, M 2016, 'Human Genetic Variability Contributes to Postoperative Morphine Consumption', Journal of Pain, vol. 17, no. 5, pp. 628-636. https://doi.org/10.1016/j.jpain.2016.02.003
De Gregori M, Diatchenko L, Ingelmo PM, Napolioni V, Klepstad P, Belfer I et al. Human Genetic Variability Contributes to Postoperative Morphine Consumption. Journal of Pain. 2016 May 1;17(5):628-636. https://doi.org/10.1016/j.jpain.2016.02.003
De Gregori, Manuela ; Diatchenko, Luda ; Ingelmo, Pablo M. ; Napolioni, Valerio ; Klepstad, Pal ; Belfer, Inna ; Molinaro, Valeria ; Garbin, Giulia ; Ranzani, Guglielmina N. ; Alberio, Giovanni ; Normanno, Marco ; Lovisari, Federica ; Somaini, Marta ; Govoni, Stefano ; Mura, Elisa ; Bugada, Dario ; Niebel, Thekla ; Zorzetto, Michele ; De Gregori, Simona ; Molinaro, Mariadelfina ; Fanelli, Guido ; Allegri, Massimo. / Human Genetic Variability Contributes to Postoperative Morphine Consumption. In: Journal of Pain. 2016 ; Vol. 17, No. 5. pp. 628-636.
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