Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery

Kenichi Fukuda, Masakazu Hayashida, Soichiro Ide, Naoko Saita, Yoshihiko Kokita, Shinya Kasai, Daisuke Nishizawa, Yasukazu Ogai, Junko Hasegawa, Makoto Nagashima, Megumi Tagami, Hiroshi Komatsu, Ichiro Sora, Hisashi Koga, Yuzuru Kaneko, Kazutaka Ikeda

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

Abstract

Individual differences in sensitivity to fentanyl, a widely used opioid analgesic, can hamper effective pain treatment. Still controversial is whether the single nucleotide polymorphisms (SNPs) of the human OPRM1 gene encoding the μ-opioid receptor influence the analgesic effects of opioids. We examined associations between fentanyl sensitivity and the two SNPs, A118G and IVS3+A8449G, in the human OPRM1 gene in 280 Japanese patients undergoing painful orofacial cosmetic surgery, including bone dissection. Regarding the A118G SNP in exon 1, in a cold pressor-induced pain test before surgery, less analgesic effects of fentanyl were shown in subjects carrying the minor G allele of the A118G SNP (median of difference between pain perception latencies before and after fentanyl injection [PPLpost-PPLpre]: 12 s) compared with subjects not carrying this allele (PPLpost-PPLpre: 15 s, p = 0.046). Furthermore, the IVS3+A8449G SNP in intron 3, which represents a complete linkage disequilibrium block with more than 30 SNPs from intron 3 to the 3′ untranslated region, was associated with 24-h postoperative fentanyl requirements. Subjects carrying the minor G allele of the IVS3+A8449G SNP required significantly less fentanyl for 24-h postoperative pain control (median: 1.5 μg/kg) compared with subjects not carrying this allele (median: 2.5 μg/kg, p = 0.010). Although further validation is needed, the present findings shed light on the involvement of OPRM1 3′ untranslated region polymorphisms in fentanyl sensitivity in addition to the A118G SNP and open new avenues for personalized pain treatment with fentanyl.

Original languageEnglish
Pages (from-to)194-201
Number of pages8
JournalPain
Volume147
Issue number1-3
DOIs
Publication statusPublished - 2009 Dec 15

Keywords

  • Association study
  • Fentanyl
  • Pain
  • Perioperative analgesia
  • Single nucleotide polymorphism
  • μ-Opioid receptor

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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