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遺伝的個人差に基づくオピオイド鎮痛薬によるがん疼痛緩和

Research Project

Project/Area Number 18014003
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTohoku University

Principal Investigator

曽良 一郎  Tohoku University, 大学院・医学系研究科, 教授 (40322713)

Co-Investigator(Kenkyū-buntansha) 富田 博秋  東北大学, 大学院医学系研究科, 助教授 (90295064)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords癌 / ゲノム / 遺伝子 / 薬理学 / 脳・神経
Research Abstract

がん疼痛を含む末梢神経障害疼痛の緩和は患者のQOLの改善に有用である。モルヒネを代表とするオピオイド類は強力な鎮痛効果をもち、がん疼痛患者の第一選択薬である。一方で嘔気・便秘・依存・耐性等の副作用が治療の大きな妨げとなっている。オピオイドの鎮痛効果や副作用には個人差が存在し、様々な遺伝子多型が関係していると考えられる。副作用や鎮痛効果と遺伝子多型との関連を明らかにすることは、個々人にあったテーラーメイド医療の確立に役立つと考えられる。そこで、我々は本研究において、オピオイド投与中のがん疼痛患者を対象に、オピオイド標的受容体であるμオピオイド受容体遺伝子(OPRM1)・δオピオイド受容体遺伝子(OPRD1)・Kオピオイド受容体遺伝子(OPRK1)およびオピオイドの嘔気と関連のあるドーパミンD2受容体遺伝子(DRD2)の一塩基多型(singlenucleotide polymorphism:SNP)が、主観的な痛みの強さや、副作用の強さに影響するか検討した。その結果、オキシコドン投与群では、DRD2の多型で、食欲不振の強さと有意な関連を認めた。一方、モルヒネ投与群では、OPRD1の多型で、痛みの改善率と有意な関連があり、OPRKIの多型で、神経因性疼痛の強さ、BPIの平均値と有意な関連を認めた。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (20 results)

All 2008 2007 2006

All Journal Article (13 results) (of which Peer Reviewed: 3 results) Presentation (6 results) Book (1 results)

  • [Journal Article] The distinctive effects of acute and chronic psychological stress on airway inflammation in a murine model of allergic asthma.2007

    • Author(s)
      Okuyama K, et. al.
    • Journal Title

      Allergology International. 56(1)

      Pages: 29-35

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Knockout of the mu opioid receptor enhances the survival of adult-generated hippocampal granule cell neurons.2007

    • Author(s)
      Harburg GC, et. al.
    • Journal Title

      Neuroscience. 144(1)

      Pages: 77-87

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mu opioid receptor regulation of ethanol-induced dopamine response in the ventral striatum: evidence of genotype specific sexual dimorphic epistasis.2007

    • Author(s)
      Job MO, et. al.
    • Journal Title

      Biol Psychiatry. 62(6)

      Pages: 627-634

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 薬物依存の分子病態.2007

    • Author(s)
      曽良一郎
    • Journal Title

      実験医学 25(13)

      Pages: 179-184

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Knockout of the mu opioid receptor enhances the survival of adult-generated hippocampal granule cell neurons.2007

    • Author(s)
      Harburg GC
    • Journal Title

      Neuroscience 144(1)

      Pages: 77-87

    • Related Report
      2006 Annual Research Report
  • [Journal Article] dextro- and levo-morphine attenuate opioid delta and kappa receptor agonist produced analgesia in mu-opioid receptor knockout mice.2006

    • Author(s)
      Wu HE, et al.
    • Journal Title

      Eur J Pharmacol 531(1-3)

      Pages: 103-107

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Morphine can produce analgesia via spinal kappa opioid receptors in the absence of mu opioid receptors.2006

    • Author(s)
      Eur J Pharmacol
    • Journal Title

      Brain Research 1083

      Pages: 61-69

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Involvement of the 3' non-coding region of the mu opioid receptor gene in morhine-induced analgesia.2006

    • Author(s)
      Kasai S, et al.
    • Journal Title

      Psychiatry Clin Neurosci 60

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Intracisternal A-Particle Element in the 3' Noncoding Region of the Mu Opioid Receptor Gene in CXBK Mice : A New Genetic Mechanism Underlying Differences in Opioid Sensitivity.2006

    • Author(s)
      Han W, et al.
    • Journal Title

      Pharmacogenetics and Genomics 16(6)

      Pages: 451-460

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association analysis of delta-opioid receptor gene polymorphisms in methamphetamine dependence/psychosis.2006

    • Author(s)
      Kobayashi H, et al.
    • Journal Title

      Am J Med Genet 141B

      Pages: 482-486

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased body weight in mice lacking mu-opioid receptors.2006

    • Author(s)
      Han W, et al.
    • Journal Title

      Neuroreport 17(9)

      Pages: 941-944

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Linkage disequilibrium and association with methamphetamine dependence/psychosis of mu-opioid receptor gene polymorphisms.2006

    • Author(s)
      Ide S, et al.
    • Journal Title

      Pharmacogenomics J 6(3)

      Pages: 179-188

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mu opioid receptor-dependent and independent components in effects of tramadol.2006

    • Author(s)
      Ide S, et al.
    • Journal Title

      Neuropsychopharmacology 51(3)

      Pages: 651-658

    • Related Report
      2006 Annual Research Report
  • [Presentation] Decreased psychosocial stress response in mu opioid receptor knockout mice.2008

    • Author(s)
      Komatsu H, et. al.
    • Organizer
      The 1st International Conference of Tohoku Neuroscience GCOE
    • Place of Presentation
      Zao
    • Related Report
      2007 Annual Research Report
  • [Presentation] Chronic social defeat stress induced behavioral and neurochemical changes in mu opioid receptor knockout mice.2007

    • Author(s)
      Komatsu H, et. al.
    • Organizer
      The Society for Neuroscience (SFN) 37th Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      2007-11-07
    • Related Report
      2007 Annual Research Report
  • [Presentation] muオピオイド受容体遺伝子欠損マウスを用いた麻薬拮抗性鎮痛薬の抗侵害受容作用の評価.2007

    • Author(s)
      井手聡一郎, その他
    • Organizer
      第28回鎮痛薬・オピオイドペプチドシンポジウム(JNRC)
    • Place of Presentation
      札幌
    • Year and Date
      2007-09-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] オピオイド感受性の遺伝的個人差.2007

    • Author(s)
      曽良一郎
    • Organizer
      第28回鎮痛薬・オピオイドペプチドシンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2007-08-31
    • Related Report
      2007 Annual Research Report
  • [Presentation] Prediction of individual sensitivity to opiates by gene analyses.2007

    • Author(s)
      Ikeda K, et. al.
    • Organizer
      5th International Receptor Symposium 2007, Development of Novel Therapy to Specific Disease in Organ.
    • Place of Presentation
      Shizuoka
    • Related Report
      2007 Annual Research Report
  • [Presentation] Chronic social defeat stress におけるオピオイド神経伝達の役割.2007

    • Author(s)
      小松浩, その他
    • Organizer
      第29回日本生物学的精神医学会・第37回日本神経精神薬理学会
    • Place of Presentation
      札幌
    • Related Report
      2007 Annual Research Report
  • [Book] オピオイド受容体Opioid receptor. In: KEY WORD精神, 第4版2007

    • Author(s)
      曽良一郎
    • Publisher
      先端医学社
    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2018-03-28  

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