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Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl.
Mol Pain. 2014 Dec 03; 10:75.MP

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.

Authors+Show Affiliations

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableAddictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. ikeda-kz@igakuken.or.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25472448

Citation

Ide, Soichiro, et al. "Haplotypes of P2RX7 Gene Polymorphisms Are Associated With Both Cold Pain Sensitivity and Analgesic Effect of Fentanyl." Molecular Pain, vol. 10, 2014, p. 75.
Ide S, Nishizawa D, Fukuda K, et al. Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl. Mol Pain. 2014;10:75.
Ide, S., Nishizawa, D., Fukuda, K., Kasai, S., Hasegawa, J., Hayashida, M., Minami, M., & Ikeda, K. (2014). Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl. Molecular Pain, 10, 75. https://doi.org/10.1186/1744-8069-10-75
Ide S, et al. Haplotypes of P2RX7 Gene Polymorphisms Are Associated With Both Cold Pain Sensitivity and Analgesic Effect of Fentanyl. Mol Pain. 2014 Dec 3;10:75. PubMed PMID: 25472448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl. AU - Ide,Soichiro, AU - Nishizawa,Daisuke, AU - Fukuda,Ken-ichi, AU - Kasai,Shinya, AU - Hasegawa,Junko, AU - Hayashida,Masakazu, AU - Minami,Masabumi, AU - Ikeda,Kazutaka, Y1 - 2014/12/03/ PY - 2014/07/14/received PY - 2014/11/18/accepted PY - 2014/12/5/entrez PY - 2014/12/5/pubmed PY - 2015/8/19/medline SP - 75 EP - 75 JF - Molecular pain JO - Mol Pain VL - 10 N2 - 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. SN - 1744-8069 UR - https://www.unboundmedicine.com/medline/citation/25472448/Haplotypes_of_P2RX7_gene_polymorphisms_are_associated_with_both_cold_pain_sensitivity_and_analgesic_effect_of_fentanyl_ L2 - http://journals.sagepub.com/doi/full/10.1186/1744-8069-10-75?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -