The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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The Influence of Genotype Polymorphism on Morphine Analgesic Effect for Postoperative Pain in Children

  • Lee, Mi Geum (Department of Anesthesiology and Pain Medicine, Gachon University Gil Medical Center) ;
  • Kim, Hyun Jung (Department of Anesthesiology and Pain Medicine, Jeju National University School of Medicine) ;
  • Lee, Keun Hwa (Department of Microbiology and Immunology, Jeju National University School of Medicine) ;
  • Choi, Yun Suk (Department of Anesthesiology and Pain Medicine, Jeju National University School of Medicine)
  • Received : 2015.08.26
  • Accepted : 2015.11.13
  • Published : 2016.01.01
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Abstract

Background: Although opioids are the most commonly used medications to control postoperative pain in children, the analgesic effects could have a large inter-individual variability according to genotypes. The aim of this study was to investigate the association between single nucleotide polymorphisms and the analgesic effect of morphine for postoperative pain in children. Methods: A prospective study was conducted in 88 healthy children undergoing tonsillectomy, who received morphine during the operation. The postoperative pain score, frequency of rescue analgesics, and side effects of morphine were assessed in the post-anesthesia care unit. The children were genotyped for OPRM1 A118G, ABCB1 C3435T, and COMT Val158Met. Results: Children with at least one G allele for OPRM1 (AG/GG) had higher postoperative pain scores compared with those with the AA genotype at the time of discharge from the post-anesthesia care unit (P = 0.025). Other recovery profiles were not significantly different between the two groups. There was no significant relationship between genotypes and postoperative pain scores in analysis of ABCB1 and COMT polymorphisms. Conclusions: Genetic polymorphism at OPRM1 A118G, but not at ABCB1 C3435T and COMT Val158Met, influences the analgesic effect of morphine for immediate acute postoperative pain in children.

Keywords

References

  1. Association of Paediatric Anaesthetists of Great Britain and Ireland. Good practice in postoperative and procedural pain management, 2nd edition. Paediatr Anaesth 2012; 22 Suppl 1: 1-79.
  2. Dahmani S, Dupont H, Mantz J, Desmonts JM, Keita H. Predictive factors of early morphine requirements in the post-anaesthesia care unit (PACU). Br J Anaesth 2001; 87: 385-9. https://doi.org/10.1093/bja/87.3.385
  3. Wu WD, Wang Y, Fang YM, Zhou HY. Polymorphism of the micro-opioid receptor gene (OPRM1 118A>G) affects fentanyl-induced analgesia during anesthesia and recovery. Mol Diagn Ther 2009; 13: 331-7. https://doi.org/10.1007/BF03256337
  4. Oertel BG, Schmidt R, Schneider A, Geisslinger G, Lotsch J. The mu-opioid receptor gene polymorphism 118A> G depletes alfentanil-induced analgesia and protects against respiratory depression in homozygous carriers. Pharmacogenet Genomics 2006; 16: 625-36. https://doi.org/10.1097/01.fpc.0000220566.90466.a2
  5. Chou WY, Wang CH, Liu PH, Liu CC, Tseng CC, Jawan B. Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology 2006; 105: 334-7. https://doi.org/10.1097/00000542-200608000-00016
  6. Sadhasivam S, Chidambaran V, Olbrecht VA, Esslinger HR, Zhang K, Zhang X, et al. Genetics of pain perception, COMT and postoperative pain management in children. Pharmacogenomics 2014; 15: 277-84. https://doi.org/10.2217/pgs.13.248
  7. De Gregori M, Garbin G, De Gregori S, Minella CE, Bugada D, Lisa A, et al. Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain. Eur J Clin Pharmacol 2013; 69: 1651-8. https://doi.org/10.1007/s00228-013-1523-7
  8. Hajj A, Peoc'h K, Laplanche JL, Jabbour H, Naccache N, Abou Zeid H, et al. Genotyping test with clinical factors: better management of acute postoperative pain? Int J Mol Sci 2015; 16: 6298-311. https://doi.org/10.3390/ijms16036298
  9. Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurs 1997; 23: 293-7.
  10. Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. BMJ 1974; 2: 656-9. https://doi.org/10.1136/bmj.2.5920.656
  11. Aldrete JA. The post-anesthesia recovery score revisited. J Clin Anesth 1995; 7: 89-91. https://doi.org/10.1016/0952-8180(94)00001-K
  12. Lotsch J. Basic genetic statistics are necessary in studies of functional associations in anesthesiology. Anesthesiology 2007; 107: 168-9. https://doi.org/10.1097/01.anes.0000268501.61048.18
  13. Chidambaran V, Mavi J, Esslinger H, Pilipenko V, Martin LJ, Zhang K, et al. Association of OPRM1 A118G variant with risk of morphine-induced respiratory depression following spine fusion in adolescents. Pharmacogenomics J 2015; 15: 255-62. https://doi.org/10.1038/tpj.2014.59
  14. Mamie C, Rebsamen MC, Morris MA, Morabia A. First evidence of a polygenic susceptibility to pain in a pediatric cohort. Anesth Analg 2013; 116: 170-7. https://doi.org/10.1213/ANE.0b013e31826f0637
  15. Oertel BG, Kettner M, Scholich K, Renne C, Roskam B, Geisslinger G, et al. A common human micro-opioid receptor genetic variant diminishes the receptor signaling efficacy in brain regions processing the sensory information of pain. J Biol Chem 2009; 284: 6530-5. https://doi.org/10.1074/jbc.M807030200
  16. Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A 1998; 95: 9608-13. https://doi.org/10.1073/pnas.95.16.9608
  17. Zhang Y, Wang D, Johnson AD, Papp AC, Sadee W. Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem 2005; 280: 32618-24. https://doi.org/10.1074/jbc.M504942200
  18. Ono T, Muto A, Kaneda T, Arita E, Yoshida T. Novel linkage disequilibrium of single nucleotide polymorphisms in the transcriptional regulatory region of micro-opioid receptor gene in Japanese population. Biol Pharm Bull 2009; 32: 721-3. https://doi.org/10.1248/bpb.32.721
  19. Kim KM. Opioid pharmacogenetics in anesthesia and pain management. Anesth Pain Med 2015; 10: 65-76. https://doi.org/10.17085/apm.2015.10.2.65
  20. Lee SH, Kim JD, Park SA, Oh CS, Kim SH. Effects of ${\mu}$-Opioid receptor gene polymorphism on postoperative nausea and vomiting in patients undergoing general anesthesia with remifentanil: double blinded randomized trial. J Korean Med Sci 2015; 30: 651-7. https://doi.org/10.3346/jkms.2015.30.5.651
  21. Brinkmann U. Functional polymorphisms of the human multidrug resistance (MDR1) gene: correlation with P glycoprotein expression and activity in vivo. Novartis Found Symp 2002; 243: 207-10.
  22. Meineke I, Freudenthaler S, Hofmann U, Schaeffeler E, Mikus G, Schwab M, et al. Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine. Br J Clin Pharmacol 2002; 54: 592-603.
  23. Berthele A, Platzer S, Jochim B, Boecker H, Buettner A, Conrad B, et al. COMT Val108/158Met genotype affects the mu-opioid receptor system in the human brain: evidence from ligand-binding, G-protein activation and preproenkephalin mRNA expression. Neuroimage 2005; 28: 185-93. https://doi.org/10.1016/j.neuroimage.2005.05.030
  24. Jimenez N, Anderson GD, Shen DD, Nielsen SS, Farin FM, Seidel K, et al. Is ethnicity associated with morphine's side effects in children? Morphine pharmacokinetics, analgesic response, and side effects in children having tonsillectomy. Paediatr Anaesth 2012; 22: 669-75. https://doi.org/10.1111/j.1460-9592.2012.03844.x

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