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The involvement of cytokines in the signal transmission mechanism between immune system and central nervous system -Using the inflammatory hyperalgesia model-

Research Project

Project/Area Number 15591656
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

IBUKI Takae  Kyoto Prefectural University of Medicine, Anesthesiology, Associate Professor, 医学研究科, 講師 (90232587)

Co-Investigator(Kenkyū-buntansha) HIROSE Munetaka  Kyoto Prefectural University of Medicine, Anesthesiology, Assistant Professor, 医学研究科, 助手 (50275228)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordscytokine / inflammatory hyperalgesia / signal transmission / prostaglandin / cyclooxygenase / フォスフォリパーゼA_2 / 末梢性炎症 / 痛覚過敏
Research Abstract

Our primary purpose of this research was to investigate the mechanism of prostaglandin-related central sensitization during inflammatory hyperalgesia by using the rat model of peripheral inflammation induced by carrageenan.
Results have shown that enzymes essential for the synthesis of prostaglandin E_2 (PG E_2) ; cyclooxygenase 2 (COX-2) and membrane-type PGE synthase (mPGES) were expressed in vascular endothelial cells throughout the central nervous system without regional differences. In most of these vascular endothelial cells, these enzymes were co-localized in the nuclei. MPGES mRNA was also detected in these cells by in situ hybridization. The time course of COX-2 and mPGES expression in vascular endothelial cells, PGE_2 synthesis and release to the cerebrospinal fluid and behavioral hyperalgesia correlated very well. Intrathecal injection of selective COX-2 inhibitor alleviated hyperalgesia in the late phase. It was strongly suggested that these vascular endothelial cells may have a key role in the activation of central nervous system induced by peripheral inflammation.
The secondary aim of this research was to identify the molecule that is involved in the inflammatory signal transmission from the peripheral inflammatory site to the central nervous system. First, we measured the serum level of various proinflammatory cytokines in the same model. Interleukin 6 (IL-6) but not IL-1 or tumor necrosis factor was significantly elevated in the plasma 3 hrs following carrageenan injection. Pretreatment of rats with IL-6 neutralizing enzyme inhibited the expression of COX-2 and mPGES in vascular endothelial cells in the central nervous system, suppressed the ex vivo release of PGE_2, and partially alleviated behavioral hyperalgesia. These results highly suggest the possibility of circulating IL-6 as a messenger molecule that transmits inflammatory information from the peripheral inflammatory site to the central nervous system.

Report

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

    (9 results)

All 2004 2003 Other

All Journal Article (8 results) Publications (1 results)

  • [Journal Article] Transmission mechanism of inflammatory signal to the central nervous system International symposium on spinal cord sciences, Neuroplasticity and stem cell treatment in spinal cord injury2004

    • Author(s)
      Ibuki T
    • Journal Title

      日本臨床麻酔学会会誌 24(1)

      Pages: 58-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Burn injury enhances brain prostaglandin E2 production through induction of cyclooxygenase-2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats2004

    • Author(s)
      Ozaki-Okayama Y, Matsumura K, Ibuki T, Ueda M, Yamazaki Y, Tanaka Y. Kobavashi S
    • Journal Title

      Critical Care Medicine 32(3)

      Pages: 795-800

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transmission mechanism of inflammatory signal to the central nervous system International symposium on spinal cord sciences, Neuroplasticity and stem cell treatment in spinal cord injury2004

    • Author(s)
      Ibuki T
    • Journal Title

      Nihon Rinsho Masuigakkaishi 24(1)

      Pages: 58-59

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Burn injury enhances brain prostaglandin E2 production through induction of cyclooxygenase-2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats2004

    • Author(s)
      Ozaki-Okayama Y, Matsumura K, Ibuki T, Ueda M, Yamazaki Y, Tanaka Y, Kobayashi S
    • Journal Title

      Critical Care Medicine 32(3)

      Pages: 795-800

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Spinal amino acid release and repeated withdrawal in spinal morphine tolerant rats2003

    • Author(s)
      Ibuki T, Marsala M, Masuyama T, Yaksh TL
    • Journal Title

      British Journal of Pharmacology 138

      Pages: 689-697

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The effects of neurosurgical stress on peripheral lymphocyte subpopulations2003

    • Author(s)
      Hori Y, Ibuki T, Hosokawa T, Tanaka
    • Journal Title

      Journal of Clinical Anesthesia 15

      Pages: 1-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cycooxygenase-2 is induced in the endothelial cells throughout the central nervous system during carrageenan-induced hind paw inflammation ; its possible role in hyperalgesia2003

    • Author(s)
      Ibuki T, Matsumura K, Yamazaki Y, Nozaki T, Tanaka Y, Kobayashi S
    • Journal Title

      Journal of Neurochemistry 86

      Pages: 318-328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The effects of neurosurgical stress on peripheral lymphocyte subpopulations2003

    • Author(s)
      Hori Y, Ibuki T, Hosokawa T, Tanaka Y
    • Journal Title

      Journal of Clinical Anesthesia 15, 1

      Pages: 1-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Y.Ozaki-Okayama, K.Matsumura, T.Ibuki.et al.: "Burn injury enhances brain prostaglandin E_2 production through induction of cyclooxy genase-2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats"Criteical Care Medicine. 32,3. 795-800 (2004)

    • Related Report
      2003 Annual Research Report

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

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