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Clarification of mechanisms of analgesia and immobility induced by general anesthesia, and exploration of new anesthetic methods

Research Project

Project/Area Number 18592037
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionHiroshima University

Principal Investigator

IRIFUNE Masahiro  Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (10176521)

Co-Investigator(Kenkyū-buntansha) KAWAHARA Michio  Hiroshima University, Graduate School of Biomedical Sciences, Professor (30034094)
DOHI Toshihiro  Hiroshima University, Graduate School of Biomedical Sciences, Professor (00034182)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,810,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsGeneral Anesthesia / Behavioral pharmacology / μ-Opioid receptor agonist / α_2-Adrenergic receptor agonist / Glycine transporter inhibitor / Unconsciousness / Immobility / Analgesia / α2-アドレナリン受容体作動薬 / 全身麻痺作用
Research Abstract

The role of μ-opioid, α_2-adrenergic, and glycine receptors in general anesthetic action was examined in mice. All drugs were administered intraperitoneally. General anesthetic action was evaluated using three end points: 1) loss of righting reflex (LORR; as a measure of unconsciousness), 2) loss of movement in response to noxious stimulation (as a measure of immobility), and 3) loss of nociceptive response (as a measure of analgesia). Gabaculine, which is a γ-aminobutyric acid (GABA)-transaminase inhibitor that increases endogenous GABA in the brain, dose-dependently induced LORR. However, even a large dose produced no immobility. Both the μ-opioid receptor agonist morphine and the α_2-adrenergic receptor agonist dexmedetomidine dose-dependently induced analgesia. In addition, both morphine and dexmedetomidine in combination with gabaculine produced immobility in a dose-dependent fashion. However, glycine transporter inhibitors did not affect immobility. These findings suggest that LORR is associated with enhanced GABA activity, and immobility is involved in μ-opioid and α_2-adrenergic receptors, but not glycine receptors.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (12 results)

All 2008 2007 2006

All Journal Article (9 results) (of which Peer Reviewed: 4 results) Presentation (3 results)

  • [Journal Article] Riluzole, a glutamate release inhibitor, induces loss of righting reflex, antinociception, and immobility in response to noxious stimulation in mice.2007

    • Author(s)
      Irifune M, et. al.
    • Journal Title

      Anesth Analg 104(6)

      Pages: 1415-1421

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Increased γ-aminobutyric acid levels in mouse brain induce loss of righting reflex, but not immobility, in response to noxious stimulation.2007

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

      Anesth Analg 104(6)

      Pages: 1422-1429

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] MK-801 enhances gabaculine-induced loss of the righting reflex in mice, but not immobility.2007

    • Author(s)
      Irifune M, et. al.
    • Journal Title

      Can J Anesth 54(12)

      Pages: 998-1005

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Riluzole, a glutamate release inhibitor, induces loss of righting reflex, antinociception, and immobility in response to noxious stimulation in mice2007

    • Author(s)
      Irifune, M., Kikuchi, N., Saida, T., Takarada, T., Shimizu, Y., Endo, C., Morita, K., Dohi, T., Sato, T., Kawahara, M
    • Journal Title

      Anesth Analg 104(6)

      Pages: 1415-21

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Increased gamma-aminobutyric acid levels in mouse brain induce loss of righting reflex, but not immobility, in response to noxious stimulation2007

    • Author(s)
      Katayama, S., Irifune, M., Kikuchi, N., Takarada, T., Shimizu, Y., Endo, C., Takata, T., Debi, T., Sato, T., Kawahara, M
    • Journal Title

      Anesth Analg 104(6)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] MK-801 enhances gabaculine-induced loss of the righting reflex in mice, but not immobility2007

    • Author(s)
      Irifune, M., Katayama, S., Takarada, T., Shimizu, Y., Endo, C., Takata, T., Morita, K., Dohi, T., Sato, T., Kawahara, M
    • Journal Title

      Can J Anaesth 54(12)

      Pages: 998-1005

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] MK-801 enhances gabaculine-induced loss of the righting reflex in mice, but not immobility.2007

    • Author(s)
      Irifune M, et. al.
    • Journal Title

      Can J Anaesth 54(12)

      Pages: 998-1005

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Riluzole, a Glutamate Release Inhibitor, Induces Loss of Righting Reflex, Antinociception, and Immobility in Response to Noxious Stimulation in Mice2007

    • Author(s)
      Masahiro Irifune
    • Journal Title

      Anesthesia & Analgesia 104・5(in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased γ-Aminobutyric Acid (GABA) Levels in Mouse Brain Induce Loss of Righting Reflex, but Not Immobility in Response to Noxious Stimulation2007

    • Author(s)
      Sohtaro Katayama
    • Journal Title

      Anesthesia & Analgesia 104・6(in press)

    • Related Report
      2006 Annual Research Report
  • [Presentation] ラット一次求心性神経からのサブスタンスP遊離に及ぼす全身麻酔薬の影響2008

    • Author(s)
      鬼塚千織子, 他.
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜会議センター
    • Year and Date
      2008-03-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] The involvement of mu-opioid and alpha(2)-adrenergic receptors in inducing immobility as one of anesthetic components2007

    • Author(s)
      Onitsuka, C., Irifune, M., Morita, K., et. al.
    • Organizer
      The 80th Annual Meeting of The Japanese Pharmacological Society
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2007-03-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 選択的N-methyl-D-aspartate(NMDA)受容体チャネル遮断薬MK-801の全身麻酔作用の検討2006

    • Author(s)
      入舩正浩, 他
    • Organizer
      第34回日本歯科麻酔学会総会・学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2006-10-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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