A clinical study to investigate effects of various genomic single nucleotide polymorphisms (SNPs) on analgesic and adverse effects of opioid analgesics

• Project/Area Number: 22591747
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Juntendo University (2011-2012); Saitama Medical University (2010)
• Principal Investigator: HAYASHIDA Masakazu 順天堂大学, 医学部, 臨床教授 (80251289)
• Co-Investigator(Renkei-kenkyūsha): YAMAGUCHI Shigeki 埼玉医科大学, 医学部, 教授 (30254220) ; IKEDA Kazutaka 東京都医学総合研究所, 参事研究員 (60281656)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 遺伝子多型 / 麻薬 / オピオイド / 術後痛 / 神経障害性疼痛 / 疼痛管理 / 麻薬感受性 / 麻薬必要量 / 麻薬副作用 / オピオイド受容体 / 疼痛管理学 / 手術痛 / 難治性慢性疼痛 / 疼痛感受性

Research Abstract

In the current study, we reconfirmed that a single nucleotide polymorphism (SNP), 118A/G of the human μ -opioid receptor gene decreased opioid sensitivity and increased postoperative opioid requirements. We also found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3 -2q34 were strongly associated with postoperative opioid requirements. The C allele of the SNP, rs2952768, was associated with more analgesic requirements. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence.

Research Products

• [Journal Article] Genome-wide association study identifies a potent locus associated with human opioid sensitivity. (2014)
  • Author(s): Nishizawa D, Fukuda K, Kasai S, Hasegawa J, Aoki Y, Nishi A, Saita N, Koukita Y, Nagashima M, Katoh R, Satoh Y, Tagami M, Higuchi S, Ujike H, Ozaki N, Inada T, Iwata N, Sora I, Iyo M, Kondo N, Won MJ, Naruse N, Uehara-Aoyama K, Itokawa M, Koga M, Arinami T, Kaneko Y, Hayashida M, Ikeda K.
  • Journal Title: Mol Psychiatry Volume: 19(1) Issue: 1 Pages: 55-62
  • DOI: 10.1038/mp.2012.164
  • Peer Reviewed
• [Journal Article] Antiemetic effect of naloxone in combination with dexamethasone and droperidol in patients undergoing laparoscopic gynecological surgery (2013)
  • Author(s): Kasagi Y, Hayashida M, Sugasawa Y, Kikuchi I, Yamaguchi K, Okutani R, Takeda S, Inada E
  • Journal Title: J Anesth Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies a potent locus associated with human opioid sensitivity (2012)
  • Author(s): Nishizawa D, Fukuda K, Kasai S, Hasegawa J, Aoki Y, Nishi A, Saita N, Koukita Y, Nagashima M, Katoh R, Satoh Y, Tagami M, Higuchi S, Ujike H, Ozaki N, Inada T, Iwata N, Sora I, Iyo M, Kondo N, Won MJ, Naruse N, Uehara-Aoyama K, Itokawa M, Koga M, Arinami T, Kaneko Y, Hayashida M, Ikeda K
  • Journal Title: Mol Psychiatry Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] 遺伝子多型とオピイド感受性-μ-オピオイド受容体遺伝子の A118G 多型を中心に- (2012)
  • Author(s): 林田眞和,福田謙一,西澤大輔,池田和隆
  • Journal Title: 臨床麻酔 Volume: 36 Pages: 1591-1508
• [Journal Article] 呼吸器外科・心臓外科の周術期疼痛管理 (2012)
  • Author(s): 川越いづみ,林田眞和
  • Journal Title: ペインクリニック Volume: 33 Pages: 39-48
• [Journal Article] 遺伝子多型が疼痛治療におけるオピイド必要量に及ぼす影響-μ-オピオイド受容体遺伝子の A118G 多型を中心として (2012)
  • Author(s): 林田眞和,福田謙一,西澤大輔,池田和隆
  • Journal Title: Practice of Pain Management Volume: 3 Pages: 28-31
• [Journal Article] 遺伝子多型が疼痛治療におけるオピオイド必要量に及ぼす影響 (2012)
  • Author(s): 林田眞和
  • Journal Title: Practice of of Pain Management Volume: 3 Pages: 28-31
• [Journal Article] 遺伝子多型とオピオイド感受性－μーオピオイド受容体遺伝子A118G多型を中心に (2012)
  • Author(s): 林田眞和
  • Journal Title: 臨床麻酔 Volume: 36 Pages: 1591-1598
• [Journal Article] Pentazocine-induced antinociception is mediated mainly by μ-opioid receptors and compromised by κ-opioid receptors in mice (2011)
  • Author(s): Shu H, Hayashida M, Arita H, Huang W, Zhang H, An K, Wu G, Hanaoka K
  • Journal Title: J Pharmacol Exp Ther Volume: 338 Pages: 579-87
  • Peer Reviewed
• [Journal Article] Drug challenge tests for diagnosis and treatments of intractable chronic pain (2011)
  • Author(s): Hanaoka K, Hayashida M, Arita H, Ide Y, Tagami M, Nagase M
  • Journal Title: ScienceMED Volume: 2 Pages: 279-282
• [Journal Article] Simultaneous monitoring of consciousness and hemodynamics during therapeutic total spinal anesthesia (2011)
  • Author(s): Chinzei m, Kitamura T, Oshima N, Hayashida M, Komori C, Kin N, Sekiyama H, Suzuki M, Yamada Y
  • Journal Title: Jpn J Clin Physiol Volume: 41 Pages: 209-214
  • Peer Reviewed
• [Journal Article] Pentazocine-induced antinociception is mediated mainly by μ-opioid receptors and compromised by κ-opioid receptors in mice (2011)
  • Author(s): Shu H, Hayashida M, Aria H, et al
  • Journal Title: J Pharmacol Exp Ther Volume: 338 Issue: 2 Pages: 579-587
  • DOI: 10.1124/jpet.111.179879
  • Peer Reviewed
• [Journal Article] Drug challenge tests for diagnosis and treatments of intractable chronic pain (2011)
  • Author(s): Hanaoka K, Hayashida M, Aria H, et al
  • Journal Title: Science MED Volume: 2 Pages: 279-282
• [Journal Article] Diversity of opioid requirements for postoperative pain control following oral surgery--is it affected by polymorphism of the μ-opioid receptor? (2010)
  • Author(s): Fukuda K, Hayashida M, Ikeda K, Koukita Y, Ichinohe T, Kaneko Y
  • Journal Title: Anesth Prog Volume: 57 Pages: 145-9
  • Peer Reviewed
• [Journal Article] Association between 5-hydroxytryptamine 2A receptor gene polymorphism and postoperative analgesic requirements after major abdominal surgery (2010)
  • Author(s): Aoki J, Hayashida M, Tagami M, Nagashima M, Fukuda K, Nishizawa D, Ogai Y, Kasai S, Ikeda K, Iwahashi K
  • Journal Title: eurosci Lett Volume: 479 Pages: 40-3
  • Peer Reviewed
• [Journal Article] Genetic polymorphisms and human sensitivity to opioid analgesics (2010)
  • Author(s): Nishizawa D, Hayashida M, Nagashima M, Koga H, Ikeda K
  • Journal Title: Methods Mol Biol Volume: 617 Pages: 395-420
  • Peer Reviewed
• [Journal Article] Anti-hypersensitivity effects of Shu-jing-huo-xue-tang, a Chinese herbal medicine, in CCI-neuropathic rats (2010)
  • Author(s): Shu H, Arita H, Hayashida M, Zhang L, An K, Huang W, Hanaoka K
  • Journal Title: J Ethnopharmacol Volume: 131 Pages: 464-70
  • Peer Reviewed
• [Journal Article] Association between 5-hydroxytryptamine 2A receptor gene polymorphism and postoperative analgesic requirements after major abdominal surgery. (2010)
  • Author(s): Aoki J
  • Journal Title: Neurosci Lett Volume: 479 Pages: 40-43
  • Peer Reviewed
• [Journal Article] Genetic polymorphisms and human sensitivity to opioid analgesics. (2010)
  • Author(s): Nishizawa D
  • Journal Title: Methods Mol Biol Volume: 617 Pages: 395-420
  • Peer Reviewed
• [Journal Article] Diversity of opioid requirements for postoperative pain control following oral surgery-Is it affected by polymorphism of the u-opioid receptor? (2010)
  • Author(s): Fukuda K
  • Journal Title: Anesth Prog Volume: 57 Pages: 145-149
  • Peer Reviewed
• [Presentation] 疼痛と不快情動における個人差の遺伝子メカニズム(In:シンポジウム:感覚から不快情動を生成する神経経路 (2011)
  • Author(s): 池田和隆, 西澤大輔, 林田眞和
  • Organizer: 第34回日本神経科学大会-こころの脳科学
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-17
• [Presentation] Association between GIRK3 gene polymorphisms and postoperative analgesic requirements after major abdominal surgery. (2010)
  • Author(s): Nishizawa D.
  • Organizer: 60th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: Walter E.Washington Convention Center(Washington DC)
  • Year and Date: 2010-11-05
• [Presentation] オピオイド感受性個人差と遺伝子多型 (2010)
  • Author(s): 池田和隆
  • Organizer: 第40回日本神経精神薬理学会
  • Place of Presentation: 仙台国際センター(山形県)
  • Year and Date: 2010-09-17
• [Presentation] GIRKチャネルサブユニツトGIRK3の遺伝子多型と開腹術後鎮痛との関連 (2010)
  • Author(s): 西澤大輔
  • Organizer: 第40回日本神経精神薬理学会
  • Place of Presentation: 仙台国際センター(山形県)
  • Year and Date: 2010-09-16
• [Presentation] オピオイド感受性に及ぼすミューオピオイド受容体遺伝子配列の影響 (2010)
  • Author(s): 笠井慎也
  • Organizer: 第31回鎮痛薬・オピオイドペプチドシンポジウム
  • Place of Presentation: 名古屋市立大学薬学部キャンパス薬友会館3階水野ホール(愛知県)
  • Year and Date: 2010-08-27
• [Book] オピオイドの効果に影響する遺伝子多型. 痛みのScience & Practice]シリーズ第4巻:病態・疾患別がん性痛の治療 (2013)
  • Author(s): 井関雅子(編集)
  • Publisher: 文光堂(印刷中)
• [Book] 鎮痛薬の効果の個人差, 痛みの薬物治療痛みの Science & Practice]シリーズ第3 巻:痛みの薬物治療 (2013)
  • Author(s): 山本達郎(編集)
  • Publisher: 文光堂(印刷中)
• [Book] 麻薬および類似薬.今日の治療薬(2013年版) (2013)
  • Author(s): 浦部晶夫、島田和幸、川合眞一編集
  • Publisher: 南江堂
• [Book] 麻酔薬.今日の治療薬(2013年版) (2013)
  • Author(s): 浦部晶夫、島田和幸、川合眞一編集
  • Publisher: 南江堂
• [Book] 今日の治療薬2013 (2013)
  • Author(s): 林田眞和
  • Total Pages: 16
  • Publisher: 麻薬および類似薬
• [Book] 帯状疱疹の注意すべき合併症-総論.帯状疱疹 Up-to-Date (2012)
  • Author(s): 稲田英一.林田眞和,井関雅子(編集)
  • Publisher: 診断と治療社
• [Book] 帯状疱疹後神経痛の治療-薬物療法-総論.帯状疱疹 Up-to-Date (2012)
  • Author(s): 稲田英一.林田眞和,井関雅子(編集)
  • Publisher: 診断と治療社
• [Book] 麻薬および類似薬.今日の治療薬(2012 年版) (2012)
  • Author(s): 浦部晶夫、島田和幸、川合眞一編集
  • Publisher: 南江堂
• [Book] 麻酔薬.今日の治療薬(2012年版) (2012)
  • Author(s): 浦部晶夫、島田和幸、川合眞一編集
  • Publisher: 南江堂
• [Book] 今日の治療薬2012 (2012)
  • Author(s): 林田眞和
  • Total Pages: 16
  • Publisher: 麻薬および類似薬
• [Book] 麻薬および類似薬.In:今日の治療薬(2012年版)(浦部晶夫ほか編集) (2012)
  • Author(s): 林田眞和
  • Publisher: 南江堂
• [Book] 麻酔薬.In:今日の治療薬(2012年版)(浦部晶夫ほか編集) (2012)
  • Author(s): 林田眞和
  • Publisher: 南江堂
• [Book] 麻薬および類似薬.今日の治療薬(2011 年版) (2011)
  • Author(s): 浦部晶夫、島田和幸、川合眞一編集
  • Publisher: 南江堂
• [Book] 麻酔薬.今日の治療薬(2011年版) (2011)
  • Author(s): 浦部晶夫、島田和幸、川合眞一編集
  • Publisher: 南江堂
• [Patent(Industrial Property Rights)] POMC 遺伝子解析による薬物感受性の評価方法 (2010)
  • Inventor(s): 池田和隆,笠井慎也,林田眞和,樋口進
  • Industrial Property Rights Holder: 池田和隆,笠井慎也,林田眞和,樋口進,財団法人東京都医学研究機構
  • Industrial Property Number: 2009-511918
  • Filing Date: 2010-07-29
• [Patent(Industrial Property Rights)] POMC遺伝子解析による薬物感受性の評価方法 (2010)
  • Inventor(s): 池田和隆, 笠井慎也, 林田眞和, 樋口進
  • Industrial Property Rights Holder: 池田和隆, 笠井慎也, 林田眞和, 樋口進および財団法人東京都医学研究機構
  • Industrial Property Number: 2009-511918
  • Acquisition Date: 2010-07-29