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Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl

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Title: Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl
Authors: Ide, Soichiro Browse this author →KAKEN DB
Nishizawa, Daisuke Browse this author →KAKEN DB
Fukuda, Ken-ichi Browse this author
Kasai, Shinya Browse this author →KAKEN DB
Hasegawa, Junko Browse this author
Hayashida, Masakazu Browse this author →KAKEN DB
Minami, Masabumi Browse this author →KAKEN DB
Ikeda, Kazutaka Browse this author →KAKEN DB
Keywords: P2X7 receptor
Purinergic receptor
Single-nucleotide polymorphism
Cold pain
Haplotype analysis
Perioperative analgesia
Issue Date: 3-Dec-2014
Publisher: Biomed Central
Journal Title: Molecular pain
Volume: 10
Start Page: 75
Publisher DOI: 10.1186/1744-8069-10-75
Abstract: Background: The P2X7 receptor is a member of the P2X family of adenosine 5'-triphosphate- gated cation channels. Several recent studies have demonstrated that this receptor is involved in mechanisms related to pain and inflammation. However, unknown is whether polymorphisms of the P2RX7 gene that encodes the human P2X7 receptor influence pain sensitivity and analgesic effects of opioids. The P2RX7 gene is known to be highly polymorphic. Thus, the present study examined associations between fentanyl sensitivity and polymorphisms in the P2RX7 gene in 355 Japanese patients who underwent painful orofacial cosmetic surgery. Results: We first conducted linkage disequilibrium (LD) analyses for 55 reported single-nucleotide polymorphisms (SNPs) in the region within and around the P2RX7 gene using genomic samples from 100 patients. In our samples, 42 SNPs were polymorphic, and a total of five LD blocks with six Tag SNPs (rs2708092, rs1180012, rs1718125, rs208293, rs1718136, and rs7132846) were observed. Thus, we further analyzed associations between genotypes/haplotypes of these Tag SNPs and clinical data using a total of 355 samples. In the genotype-based association study, only the rs1718125 G > A SNP tended to be associated with higher pain scores on a visual analog scale 24 h after surgery (VAS24). The haplotype-based association study showed that subjects with homozygous haplotype No. 3 (GTAAAC; estimated frequency: 15.0%) exhibited significantly higher cold pain sensitivity and lower analgesic effects of fentanyl for acute cold pain in the cold pressor test. Conversely, subjects who carried haplotype No. 1 (ACGGAC; estimated frequency: 24.5%) tended to exhibit lower cold pain sensitivity and higher analgesic effects of fentanyl. Furthermore, subjects with homozygous haplotype No. 2 (GCGGAC; estimated frequency: 22.9%) exhibited significantly lower VAS24 scores. Conclusions: Cold pain sensitivity and analgesic effects of fentanyl were related to the SNP and haplotypes of the P2RX7 gene. The patients with the rs1718125 G>A SNP tended to show higher VAS24 scores. Moreover, the combination of polymorphisms from the 5'-flanking region to exon 5 recessively affected cold pain sensitivity and analgesic effects of opioids for acute cold pain. The present findings shed light on the involvement of P2RX7 gene polymorphisms in naive cold pain sensitivity and analgesic effects of fentanyl.
Type: article
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 井手 聡一郎

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