Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery
Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery
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DOI：
10.1016/j.pain.2009.09.004
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发表时间：
2009-12-15
期刊：
影响因子：
7.4
通讯作者：
Ikeda, Kazutaka
中科院分区：
文献类型：
--
作者：
Fukuda, Kenichi;Hayashida, Masakazu;Ikeda, Kazutaka
芬太尼是一种广泛使用的阿片类止痛剂，其敏感性的个体差异可能会阻碍有效的疼痛治疗。编码L阿片受体的人OPRM1基因的单核苷酸多态(SNPs)是否影响阿片类药物的镇痛作用仍存在争议。我们研究了280名接受痛苦的口腔面部整形手术的日本患者的芬太尼敏感性与人类OPRM1基因中的两个SNP，A118G和IVS3+A8449G的相关性。关于外显子1的A118G SNP，在术前冷加压痛试验中，携带A118G SNP的微小G等位基因的受试者(注射芬太尼前后疼痛潜伏期差的中位数[PPLpost-PPLpre]：12 S)与不携带该等位基因的受试者(PPLpost-PPLpre：15 S，p=0.046)相比，芬太尼的镇痛效果更差。此外，内含子3的IVS3+A8449G SNP代表了从内含子3到3‘非翻译区的30多个SNP的完整连锁不平衡块，与术后24小时芬太尼需求有关。携带IVS3+A8449GSNP的微小G等位基因的受试者在术后24小时的疼痛控制方面所需的芬太尼(中位数：1.5mUg/kg)显著低于不携带该等位基因的受试者(中位数：2.5mUg/kg，p=0.010)。虽然还需要进一步的验证，但目前的发现揭示了除了A118G SNP外，OPRM1 3‘非翻译区多态与芬太尼敏感性有关，并为芬太尼个性化疼痛治疗开辟了新的途径。(C)2009年国际疼痛研究协会。爱思唯尔出版公司版权所有。
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 l-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 mu g/kg) compared with subjects not carrying this allele (median: 2.5 mu g/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. (C) 2009 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.