Genome-wide association study to elucidate genetic pathogenesis of chronic postoperative pain

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08829
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Juntendo University
• Principal Investigator: Hayashida Masakazu 順天堂大学, 医学部, 特任教授 (80251289)
• Co-Investigator(Kenkyū-buntansha): 池田 和隆 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 分野長 (60281656) ; 西澤 大輔 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主席研究員 (80450584)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 婦人科良性疾患 / 腹腔鏡下手術 / オピオイド / 術後痛 / 遷延性術後痛 / 遺伝子多型 / ゲノムワイド関連解析

Outline of Final Research Achievements

A genome-wide association study (GWAS) was performed in 333 patients who underwent gynecologic laparoscopic surgery to investigate genetic backgrounds underlying effects of opioid analgesics on acute intraoperative and postoperative pain and the development of chronic postoperative pain. The rs7858836 C/T SNP in the Astrotactin 2 gene potentiated the analgesic effect of fentanyl on postoperative pain, and the rs1799971 A/G SNP in the μ-opioid receptor gene attenuated the analgesic effect of remifentanil on intraoperative pain. Although the incidence of prolonged postoperative pain was low (12 cases, 3.6%), and the GWAS failed to identify SNPs that could be associated with the development of chronic pain, a multicenter study using an individual gene analysis showed that the rs11726196 G/T SNP in the Transient Receptor Potential Canonical Channel 3 gene could be associated with the development of chronic pain, including chronic postoperative pain.

Free Research Field

麻酔科学、疼痛医学、遺伝学、心臓血管麻酔

Academic Significance and Societal Importance of the Research Achievements

今回の研究で、Astrotactin2遺伝子の一塩基多型(SNP)が術後フェンタニルの鎮痛効果を増強し、μ-opioid受容体遺伝子のSNPが術中レミフェンタニルの鎮痛効果を減弱させることが判明した。この結果は、我々の以前の研究も含む先行研究で得られた結果と一致し補強する所見と思われ、個別化鎮痛医療の発展に資すると考えられた。術後遷延痛も含む慢性痛の遺伝的背景に関する報告は未だに乏しいが、Transient Receptor Potential Canonicalチャネル3遺伝子のSNPの慢性術後痛への関与を見出した事は、慢性術後痛発生の病態生理解明に資する結果と思われた。