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Possible involvement of activation of spinal glia with chronic pain

Research Project

Project/Area Number 17591613
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OBATA Hideaki  Gunma University, School of Medicine, Associate professor (20302482)

Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsSpinal glia / Microglia / Astrocyte / Hyperalgesia / Allodynia / Postoperative pain / Neuropathic pain / 髄グリア / アストロ際と痛覚過敏
Research Abstract

Experiments with post-operative pain
Male Sprague-Dawley rats (250g) were used in all experiments. An incision was made on the plantar aspect of the hind paw. Mechanical hypersensitivity was measured by determining the withdrawal threshold to von Frey filaments applied to the paw. Intraperitoneral administration of selective microglial inhibitor minocycline (50 mg/kg/day for 3 d) did not inhibit mechanical hypersensitivity. 0X42 expression in the spinal cord, however, suppressed 3d after minocycline injection. Intretherecal administration of p38MAPK inhibitor SB203580 (10 μg/day for 3d) also did not inhibit mechanical hypersensitivity. In the spinal cord, p-p38MAPK expressions were colocalized in 0X42 positive cells. This means p38MAPK is only expressed in microglia. In contrast, same paradigm injection with minocycline and SB203580 inhibited mechanical allodynia in rats with neuropathic pain induced by L5 spinal nerve transection (SNT). We concluded that microglia in the spinal cord does not have important role in the post-operative pain.
Experiments with neuropathic pain All animals used in this study were male Sprague-Dawely rats (160-180g). We used L5 spinal nerve transection (SNT) model with the some modification of spinal nerve ligation model described by Kim and Chung (1992). Selective glia cell inhibitor propentofylline was infused trathecally for 7 days by an osmotic infusion pump (1 μ1/h, 7 day pump, ALZET, Cupertino, CA) initiated just after, 14 d after, or 60 days after SNT. Intrathecal infusion of propentofylline started just after SNT suppressed the development of allodynia dose-dependently (0.1, 1 and 10 μg/day). Other two paradigms did not inhibit existing allodynia. In the spinal cord, expression of astrocytes (GFAP) was always suppressed after propentofylline infusion. We concluded that astrocytes in the spinal cord play an important role in development of neuropathic pain.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (29 results)

All 2008 2007 2006 2005

All Journal Article (14 results) (of which Peer Reviewed: 4 results) Presentation (9 results) Book (6 results)

  • [Journal Article] Management of chronic pain focused on alpha2 receptors2008

    • Author(s)
      Hideaki Obata
    • Journal Title

      Shinko

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Possible involvement of spinal noradrenergic mechanisms in the anti-allodynic effect of intrathecally administered 5-HT_2c receptor agonists in the rats with peripheral nerve injury2007

    • Author(s)
      Hideaki Obata
    • Journal Title

      Eur J Pharmacol 567

      Pages: 89-94

    • 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] Possible involvement of spinal noradrenergic mechanisms in the anti-allodynic effect of intrathecally administered 5-HT_<2C> receptor agonists in the rats with peripheral nerve injury2007

    • Author(s)
      Hideaki Obata
    • Journal Title

      Eur J Pharmacol 567

      Pages: 89-94

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Technique of pain management for pain clinicians, Toyo Miyazaki editor2007

    • Author(s)
      Hideaki Obata
    • Journal Title

      Nakayama

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Alpha2-receptors in the dorsal horn of the spinal cord2007

    • Author(s)
      Hideaki Obata
    • Journal Title

      Kasseido

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Possiblξinvolvement of spinal noradrenergic mechanisms in the anti-allodyllic effbct of intrathecally administered 5-HT_2c receptor agonistsin the rats with peripheral nerve injury2007

    • Author(s)
      Hideaki Obata
    • Journal Title

      Eur J pharmacol 567

      Pages: 89-94

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spinal glial activation contribute to post-operative mechanical hyperse nsitivity in the rat2006

    • Author(s)
      Hideaki Obata
    • Journal Title

      Journal of pain 7

      Pages: 816-922

    • 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] Peripheral 5-HT2A receptor antagonism attenuates primary thermal hyperalgesia and secondary mechanical allodynia after thermal injury inrats2006

    • Author(s)
      Masayuki Sasaki
    • Journal Title

      Pain 122

      Pages: 130-136

    • 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] Spinal glial activation contribute to post-operative mechanical hypersensitivity in the rat2006

    • Author(s)
      Hideaki Obata
    • Journal Title

      J pain 7

      Pages: 816-922

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Peripheral 5-HT2A receptor antagonism attenuates primary thermal hyperalgesia and secondary mechanical allodynia after thermal injury in rats2006

    • Author(s)
      Masayuki Sasaki
    • Journal Title

      Pain 122

      Pages: 130-136

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
  • [Journal Article] Spinal glial activation contribute to post-operative mechanical hypersensitivity in the rat2006

    • Author(s)
      Hideaki Obata
    • Journal Title

      Journal of pain 7

      Pages: 816-922

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats.2005

    • Author(s)
      Shiro Koizuka, Hideaki Obata, Masayuki Sasaki, Shigeru Saito, Fumio Goto.
    • Journal Title

      Can J Anaesth 52

      Pages: 498-505

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Monoamine-mediated anti-allodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain.2005

    • Author(s)
      Hideaki Obata, Shigeru Saito, Shiro Koizuka, Koichi Nishikawa, Fumio Goto.
    • Journal Title

      Anesth Analg 100

      Pages: 1406-1410

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 下行性抑制系と慢性疼痛2005

    • Author(s)
      小幡英章
    • Journal Title

      麻酔 54

    • Related Report
      2005 Annual Research Report
  • [Presentation] Activation of astrocytes in the spinal cord contributes to bilateral development of allodynia after peripheral nerve injury in rats2007

    • Author(s)
      Hideaki Obata
    • Organizer
      Society for Neuroscience Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      2007-11-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Activation of astrbcytes in the spinal cord contributes to bilateral development of allodynia after pefipheral nerve injury in rats2007

    • Author(s)
      Hideaki Obata
    • Organizer
      Society for Neuroscience Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      2007-11-04
    • Related Report
      2007 Annual Research Report
  • [Presentation] ラット神経因性疼痛モデルに対するグリア細胞抑制薬の効果2007

    • Author(s)
      小幡英章
    • Organizer
      第29回日本疼痛学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-07-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ラット神経因在疼痛モデルに対するグリア細胞抑制薬の効果2007

    • Author(s)
      小幡 英章
    • Organizer
      日本疼痛学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-07-07
    • Related Report
      2007 Annual Research Report
  • [Presentation] Antiallonic effect of glial cell inhibitor in rats with neuropathic pain2007

    • Author(s)
      Hideaki Obata
    • Organizer
      The 29th annual meeting of the Japanese association for the study of pain
    • Place of Presentation
      Yokohama
    • Year and Date
      2007-07-04
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 脊髄グリアの活性化はラット術後痛モデルの感覚過敏に関与している2007

    • Author(s)
      小幡英章
    • Organizer
      日本麻酔科学会第54回学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2007-06-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Spinal glial activation contributes to the hypersensitivity after paw incision in rats2007

    • Author(s)
      Hideaki Obata
    • Organizer
      The 54th annual meeting of Japanese society of anesthesiologists
    • Place of Presentation
      Sapporo
    • Year and Date
      2007-06-02
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Antiallonic effect of glial cell inhibitor in rats with neuropathic pain2007

    • Author(s)
      Shinobu Sakurazawa
    • Organizer
      The 54th annual meeting of Japanese society of anesthesiologists
    • Place of Presentation
      Kobe
    • Year and Date
      2007-06-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ラット神経因性疼痛モデルに対するグリア細胞抑制薬の効果2006

    • Author(s)
      桜澤忍
    • Organizer
      日本麻酔科学会第53回学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2006-06-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] α2受容体をターゲットにした慢性疼痛の治療2008

    • Author(s)
      小幡英章
    • Total Pages
      11
    • Publisher
      真興交易図書出版部、ペインクリニックVOL.29, No.2
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] α2受容体をターゲットにした慢性疼痛の治療2008

    • Author(s)
      小幡 英章
    • Total Pages
      11
    • Publisher
      真興交易図書出版部、ペインクリニックVOL.29,No.2
    • Related Report
      2007 Annual Research Report
  • [Book] ペインクリニシャンのための痛み診療のコツと落とし穴、宮崎東洋編2007

    • Author(s)
      小幡英章
    • Total Pages
      2
    • Publisher
      中山書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 脊髄後角のα2受容体-その機能と下行性抑制系-、麻酔増刊VOL.562007

    • Author(s)
      小幡英章
    • Total Pages
      11
    • Publisher
      克誠堂出版 麻酔増刊
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] ペインクリニシャンのための痛み診療のコツと落とし穴、宮崎東洋編2007

    • Author(s)
      小幡 英章
    • Total Pages
      2
    • Publisher
      中山書店
    • Related Report
      2007 Annual Research Report
  • [Book] 脊髄後角のα2受容体-その機能と下行性抑制系-、麻酔増刊VOL.562007

    • Author(s)
      小幡 英章
    • Total Pages
      11
    • Publisher
      克誠堂出版 麻酔増刊
    • Related Report
      2007 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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