Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery.
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 mu-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]: 12s) compared with subjects not carrying this allele (PPLpost-PPLpre: 15s, 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: 1.5microg/kg) compared with subjects not carrying this allele (median: 2.5microg/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.
Department of Oral Health and Clinical Science, Division of Dental Anesthesiology (Orofacial Pain Center/Suidoubashi Hospital), Tokyo Dental College, Chiyoda-ku, Tokyo, Japan.
Kenichi
K
Fukuda
Masakazu
M
Hayashida
Soichiro
S
Ide
Naoko
N
Saita
Yoshihiko
Y
Kokita
Shinya
S
Kasai
Daisuke
D
Nishizawa
Yasukazu
Y
Ogai
Junko
J
Hasegawa
Makoto
M
Nagashima
Megumi
M
Tagami
Hiroshi
H
Komatsu
Ichiro
I
Sora
Hisashi
H
Koga
Yuzuru
Y
Kaneko
Kazutaka
K
Ikeda
D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D005260:Female; D005283:Fentanyl / Q000627:therapeutic use*; D005787:Gene Frequency; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010149:Postoperative Pain / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D018709:Statistics, Nonparametric; D013518:Surgery, Plastic / Q000009:adverse effects; D055815:Young Adult
D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D005283:Fentanyl