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Study on Efficacy and Mechanism of Herbal Medicine in Neuropathic Pain

Research Project

Project/Area Number 15591618
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionThe University of Tokyo

Principal Investigator

ARITA Hideko  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (10114357)

Co-Investigator(Kenkyū-buntansha) SEKIYAMA Hiroshi  The University of Tokyo, Faculty of Medicine, Project Lecturer, 医学部附属病院, 特任講師 (40301105)
HANAOKA Kazuo  The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (80010403)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsHerbal Medicine / Sokei-Kakketsu-to / Processed Aconiti Tuber / Mesaconitine / Lactoferrin / Morphine Tolerance / U50488H / MK-801 / ラットCCIモデル / 坐骨神経部分損傷モデル / 修治ブシ末 / 熱刺激 / 圧刺激 / 桂枝加朮附湯 / 真武湯 / 修治附子末
Research Abstract

1. Previous studies with the rat chronic constriction injury (CCI) model have shown that Sokei-kakketsu-to suppressed increased hypersensitivity to mechanical or heat stimuli ; and its mechanism of action is via noradrenergic activation of the descending inhibitory system. On the other hand, in similar studies on Keishi-ka-jutsubu-to and Shinbu-to, no suppression of increased hypersensitivity was observed.
2. Processed Aconiti tuber, a Chinese herbal medicine, suppressed increased hypersensitivity to heat or pressure stimuli dose-dependently in a rat CCI model, and it was suggested that part of the mechanism of action was via kappa-opioid receptor. Lactoferrin, administered intrathecally or intraperitoneally, also suppressed hypersensitivity to heat or mechanical stimuli, dose-dependently, and it was suggested that the action was via mu-opioid receptor. Moreover, combined administration of processed Aconiti tuber and lactoferrin, both at sub-analgesic doses, showed a hypersensitivity su … More ppressing effect, suggesting lactoferrin may enhance the hypersensitivity suppressing effect of processed Aconiti tuber.
3. The suppressing effect of processed Aconiti tuber on morphine tolerance was investigated using mice. Sub-analgesic doses of processed Aconiti tuber dose-dependently suppressed the morphine tolerance induced by cyclic administration of morphine (once a day for seven days). It was indicated that this action was mainly due to mesaconitine, a constitutive alkaloid. Even after morphine tolerance had developed, processed Aconiti tuber was shown to reverse the tolerance. Those morphine tolerance suppressing actions of processed Aconiti tuber have been proved to be via kappa-opioid receptor. Then, morphine tolerance suppressing effects were investigated regarding U50488H, a selective kappa-opioid receptor agonist, and MK-801, an NMDA receptor antagonist. U50488H inhibited development of morphine tolerance, and it also had a tolerance-reversing action on established tolerance. On the other hand, although MK-801 suppressed the development of morphine tolerance, it failed to abolish morphine tolerance that had already been established. Less

Report

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

    (13 results)

All 2006 2004 Other

All Journal Article (11 results) Patent(Industrial Property Rights) (1 results) Publications (1 results)

  • [Journal Article] Pain-relieving effects of processed Aconiti tuber in CCI-neuropathic rats.2006

    • Author(s)
      Xu H 他
    • Journal Title

      Journal of Ethnopharmacology 103

      Pages: 392-397

    • 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 processed Aconiti tuber and its ingredient alkaloids on the development of antinociceptive tolerance to morphine.2006

    • Author(s)
      Shu H 他
    • Journal Title

      Journal of Ethnopharmacology 103

      Pages: 398-405

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inhibition of morphine tolerance by processed Aconiti tuber is mediated through activation of kappa opioid receptors.2006

    • Author(s)
      Shu H 他
    • Journal Title

      Journal of Ethnopharmacology (Epub ahead of print)

      Pages: 2006-2006

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pain-relieving effects of processed Aconiti tuber in CCI-neuropathic rats.2006

    • Author(s)
      Xu H, Arita H, Hayashida M, Zhang L, Sekiyama H, Hanaoka K
    • Journal Title

      Journal of Ethnopharmacology 103

      Pages: 392-397

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of processed Aconiti tuber and its ingredient alkaloids on the development of antinociceptive tolerance to morphine.2006

    • Author(s)
      Shu H, Arita H, Hayashida M, Sekiyama H, Hanaoka K
    • Journal Title

      Journal of Ethnopharmacology 103

      Pages: 398-405

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inhibition of morphine tolerance by processed Aconiti tuber is mediated through activation of kappa opioid receptors.2006

    • Author(s)
      Shu H, Arita H, Hayashida M, Chiba S, Sekiyama H, Hanaoka K
    • Journal Title

      Journal of Ethnopharmacology Jan 27(Epub ahead of print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pain-relieving effects of processed Aconiti tuber in CCI-neuropathic rats.2006

    • Author(s)
      Xu H
    • Journal Title

      Journal of Ethnopharmacology 103

      Pages: 392-397

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effects of processed Aconiti tuber and its ingredient alkaloids on the development of antinociceptive tolerance to morphine.2006

    • Author(s)
      Shu H
    • Journal Title

      Journal of Ethnopharmacology 103

      Pages: 398-405

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of morphine tolerance by processed Aconiti tuber is mediated through activation of kappa opioid receptors.2006

    • Author(s)
      Shu H
    • Journal Title

      Journal of Ethnopharmacology (Epub ahead of print)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The Analgesic Effect of Lactferrin in a Rat of Neuropathic Pain2004

    • Author(s)
      Hideko Arita, et al.
    • Journal Title

      11th International Pain Clinic World Society of Pain Clinicians

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cc-administration of lactferin enhances the analgesic effect of processed Aconitituber in a rat model of neuropathic pain2004

    • Author(s)
      Hideko Arita, et al.
    • Journal Title

      11th International Pain Clinic World Society of Pain Clinisians

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 神経因性疼痛に対し鎮痛効果を示す新規組成物2004

    • Inventor(s)
      有田英子
    • Industrial Property Rights Holder
      株式会社NRLファーマ
    • Industrial Property Number
      2004-116192
    • Filing Date
      2004-03-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Hideko Arita: "The analgesic effect of processed aconit tuber in CCI rat."11^<th> International Pain clinic(11〜17, July, 2004), World Society of Pain Clinicians (WSPC)(学会発表). (2004)

    • Related Report
      2003 Annual Research Report

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

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