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Molecular mechanisms of the development of opioid tolerance in neuropathic pain model in mice.

Research Project

Project/Area Number 15390469
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionChiba University

Principal Investigator

YAMAMOTO Tatsuo  Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (20200818)

Co-Investigator(Kenkyū-buntansha) AOE Tomohiko  Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (90311612)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordsmorphine / tolerance / analgesia / neuropatliic pain / mouse / Bip / BiP / オピオイド / KDEL受容体 / トランスジェーニックマウス
Research Abstract

It is well known that neuropathic pain is relatively refractory to opioid therapy. The mechanisms of this refractoriness to opioids are not fully understood. Receptor protein is usually synthesized on the membrane of endoplasmic reticulum (ER), is secreted to cytoplasm, is transported to the cell membrane via Golgi body, and then act as a receptor on the cell membrane. In ER, receptor protein is folded and formed tridimensional structure. After this maturation process, receptor protein finally obtains its function as a receptor. In the present study, we investigated the role of this maturation process on the development of refractoriness to opioids of neuropathic pain. Especially, we chose Bip protein, one of the key proteins for the maturation of receptor protein, and studied the role of Bip on the development of refractoriness to opioid with Bip transgenic mice. At first, we administered morphine intraperitoneally to the Bip transgenic mice 5 days (2 times per day) and found that morphine tolerance did not develop after this morphine treatment in the Bip transgenic mice. Although we need more data, our data suggested that Bip may be involved in the development of morphine tolerance and that it is possible that Bip is one of the key protein on the development of refractoriness to opioids in the neuropathic pain patients.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (9 results)

All 2006 2005 2004 Other

All Journal Article (9 results)

  • [Journal Article] Effects of Intrathecal and Intracerebroventricular Administration of Neuropeptide W-23 and Neuropeptide B on the Mechanical Allodynia Induced by Partial Sciatic Nerve Ligation in Rats.2006

    • Author(s)
      山本達郎
    • Journal Title

      Neuroscience 137

      Pages: 265-273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of Intrathecal and Intracerebroventricular Administration of Neuropeptide W-23 and Neuropeptide B on the Mechanical Allodynia Induced by Partial Sciatic Nerve legation in Rats2006

    • Author(s)
      Yamamoto et al.
    • Journal Title

      Neuroscience 137

      Pages: 265-278

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 病的疼痛の発症メカニズム2005

    • Author(s)
      山本達郎
    • Journal Title

      ペインクリニック 26

      Pages: 1537-1544

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanisms of pathological pain.2005

    • Author(s)
      Yamamoto
    • Journal Title

      Pain Clinic 26

      Pages: 1537-1544

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antinociceptive Effects of N-Acetylaspartylglutamate (NAAG) peptidase inhibitors ZJ-11, ZJ-17 and ZJ-43 in the tat formalin test and in the rat neuropathic pain model.2004

    • Author(s)
      山本達郎
    • Journal Title

      European Journal of Neuroscience 20

      Pages: 483-494

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antinociceptive Effects of N-Acetylaspartylghitamate (NAAG) peptidase inhibitors ZJ-11, ZJ-17 and ZJ-43 in the tat formalin test and in the rat neuropathic pain model.2004

    • Author(s)
      Yamamoto et al.
    • Journal Title

      European Journal of Neuroscience 20

      Pages: 483-494

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Buprenorphine Activates μ and Opioid Receptor Like-1 Receptors Simultaneously but Analgesic Effect is Mainly Mediated by μ Receptor Activation in Rat Formalin Test

    • Author(s)
      山本達郎
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Buprenorphine Activates μ and Opioid Receptor Like-1 Receptors Simultaneously but Analgesic Effect is Mainly Mediated by μ Receptor Activation in Rat Formalin Test

    • Author(s)
      Yamamoto et al.
    • Journal Title

      Journal of Pharmacology & Experimental Therapeutics (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Buprenorphine Activates μ and Opioid Receptor Like-1 Receptors Simultaneously but Analgesic Effect is Mainly Mediated by μ Receptor Activation in Rat Formalin Test

    • Author(s)
      山本達郎
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics in press

    • Related Report
      2005 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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