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β1-肾上腺素能受体基因多态性与接受美容手术患者疼痛及芬太尼敏感性的相关性。

Association between genetic polymorphisms of the β1-adrenergic receptor and sensitivity to pain and fentanyl in patients undergoing painful cosmetic surgery.

机构信息

Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

出版信息

J Pharmacol Sci. 2013;121(1):48-57. doi: 10.1254/jphs.12159fp. Epub 2012 Dec 21.

Abstract

Individual differences in the sensitivity to fentanyl, a widely used opioid analgesic, can hamper effective pain treatment. The adrenergic system is reportedly involved in the mechanisms of pain and analgesia. Here, we focused on one of the adrenergic receptor genes, ADRB1, and analyzed the influence of single-nucleotide polymorphisms (SNPs) in the ADRB1 gene on individual differences in pain and analgesic sensitivity. We examined associations between pain and fentanyl sensitivity and the two SNPs, A145G and G1165C, in the human ADRB1 gene in 216 Japanese patients who underwent painful orofacial cosmetic surgery, including bone dissection. The patients who carried the A-allele of the A145G SNP were more sensitive to cold pressor- induced pain than those who did not carry this allele, especially in male patients. The analgesic effect was significantly less in females who carried the G-allele of the G1165C SNP than the females who did not carry the G-allele. The haplotype analysis revealed a significant decrease in 24-h postoperative fentanyl use in female 145A/1165C haplotype carriers. These results suggest that SNPs in the ADRB1 gene are associated with individual differences in pain and analgesic sensitivity, and analyzing these SNPs may promote personalized pain treatment in the future.

摘要

个体对芬太尼(一种广泛使用的阿片类镇痛药)敏感性的差异可能会妨碍有效的疼痛治疗。据报道,肾上腺素能系统参与疼痛和镇痛的机制。在这里,我们关注肾上腺素能受体基因之一 ADRB1,并分析了 ADRB1 基因中的单核苷酸多态性(SNPs)对疼痛和镇痛敏感性个体差异的影响。我们在 216 名接受疼痛性或口腔美容手术(包括骨切开术)的日本患者中检查了疼痛和芬太尼敏感性与 ADRB1 基因中的两个 SNPs(A145G 和 G1165C)之间的关联。与不携带该等位基因的患者相比,携带 A145G SNP 的 A-等位基因的患者对冷加压诱导的疼痛更敏感,尤其是男性患者。携带 G1165C SNP 的 G-等位基因的女性的镇痛效果明显低于不携带 G-等位基因的女性。单体型分析显示,女性 145A/1165C 单体型携带者的 24 小时术后芬太尼使用量显著减少。这些结果表明,ADRB1 基因中的 SNPs 与疼痛和镇痛敏感性的个体差异相关,分析这些 SNPs 可能有助于未来实现疼痛治疗的个体化。

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