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遗传多态性可能与炎症性疼痛患者的疼痛严重程度和阿片类药物剂量需求相关:临床观察研究。

Genetic Polymorphisms of Are Possibly Associated with Pain Severity and Opioid Dose Requirements in Patients with Inflammatory Pain Conditions: Clinical Observation Study.

机构信息

Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyoku, Tokyo 113-8655, Japan.

Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Kami Kitazawa 2-1-6, Setagayaku, Tokyo 156-0057, Japan.

出版信息

Int J Mol Sci. 2023 Apr 10;24(8):6986. doi: 10.3390/ijms24086986.

Abstract

Autotaxin, encoded by the gene, is a known key element of neuropathic pain; however, its involvement in nociceptive pain processing remains unclear. We explored the associations between postoperative pain intensity, 24-h postoperative opioid dose requirements, and 93 -gene single-nucleotide polymorphisms (SNPs) in 362 healthy patients who underwent cosmetic surgery using the dominant, recessive, and genotypic models. Next, we validated the associations between relevant SNPs on the one hand and pain intensity and daily opioid dosages on the other in 89 patients with cancer-related pain. In this validation study, a Bonferroni correction for multiplicity was applied on all relevant SNPs of the gene and their respective models. In the exploratory study, three models of two SNPs (rs7832704 and rs2249015) were significantly associated with postoperative opioid doses, although the postoperative pain intensity was comparable. In the validation study, the three models of the two SNPs were also significantly associated with cancer pain intensity ( < 0.017). Patients with a minor allele homozygosity complained of more severe pain compared with patients with other genotypes when using comparable daily opioid doses. Our findings might suggest that autotaxin is associated with nociceptive pain processing and the regulation of opioid requirements.

摘要

自分泌酶,由基因编码,是已知的神经性疼痛的关键因素;然而,其在伤害性疼痛处理中的参与仍不清楚。我们使用显性、隐性和基因型模型,在 362 名接受美容手术的健康患者中,探索了术后疼痛强度、24 小时术后阿片类药物剂量需求,以及 93 个基因单核苷酸多态性(SNP)之间的关联。接下来,我们在 89 名患有癌症相关疼痛的患者中,验证了相关 SNP 与疼痛强度和每日阿片类药物剂量之间的关联。在这项验证研究中,对基因和其各自模型的所有相关 SNP 进行了多重性的 Bonferroni 校正。在探索性研究中,两个 SNP(rs7832704 和 rs2249015)的三个模型与术后阿片类药物剂量显著相关,尽管术后疼痛强度相当。在验证研究中,两个 SNP 的三个模型也与癌症疼痛强度显著相关(<0.017)。与其他基因型的患者相比,具有次要等位基因纯合性的患者在使用可比的每日阿片类药物剂量时,疼痛更严重。我们的研究结果可能表明自分泌酶与伤害性疼痛处理和阿片类药物需求的调节有关。

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Endogenous opioid peptides in the descending pain modulatory circuit.下行痛觉调制回路中的内源性阿片肽。
Neuropharmacology. 2020 Aug 15;173:108131. doi: 10.1016/j.neuropharm.2020.108131. Epub 2020 May 15.

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