The involvement of cytokines in the signal transmission mechanism between immune system and central nervous system -Using the inflammatory hyperalgesia model-
| Project/Area Number |
15591656
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
IBUKI Takae Kyoto Prefectural University of Medicine, Anesthesiology, Associate Professor, 医学研究科, 講師 (90232587)
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| Co-Investigator(Kenkyū-buntansha) |
HIROSE Munetaka Kyoto Prefectural University of Medicine, Anesthesiology, Assistant Professor, 医学研究科, 助手 (50275228)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| 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)
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| Keywords | cytokine / 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 |
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| 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.
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Report
(4 results)
Research Products
(9 results)
