| Project/Area Number |
18613010
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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 |
Pain science
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| Research Institution | Kyushu University |
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Principal Investigator |
TAKE Hiro Kyushu University, Faculty of Dental Sciences, Professor (10420598)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Hiroshi KYUSHU UNIVERSITY, Faculty of Dental Sciences, Professor (20155774)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,080,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | pain / leptomeninges / inflammatory cytokines / glial cells / patch clamp / NMDA receotors / パッチクランプ / 三叉神経脊髄路核 / 下歯槽神経切断 / アストロサイト |
|---|
| Research Abstract |
After immunization with the complete Freund's adjuvant (CFA) , cyclooxygenase (COX) -2 and membrane-bound prostaglandin E synthase-1 (mPGES-1) were induced in the leptomeninges. Primary cultured leptomeningeal cells secreted PGE_2 after treatment with lipopolysaccharide (LPS) or proinflammatory cytokines. The LPS-induced release of PGE_2 was depressed by a selective COX-2 inhibitor, NS-398. On the other hand, TGF-β1 and TGF-β receptor II(TGF-βRII)both markedly increased in the leptomeninges and the parenchymal cells after the CFA injection. Double staining immunohistochemistry demonstrated TGF-β1 to be induced in both glial cells and cortical neurons, while TGF-βRII was only induced in cortical neurons. PGE_2 was found to directly increase the production of TGF-β1 and TGF-βRII in the primary cultured cells. These observations strongly suggest that PGE_2, which is biosynthesized by the leptomeninges, mainly regulates the production of TGF-β1 by glial cells and cortical neuron, thus playing a protective role in the cortical neurons during systemic inflammation. Furthermore, we found that IL-1β increased the neuronal excitability by inhibition of ChTX-sensitive K^ca channels activated by Ca^ (2+) influx through both NMDA receptors and voltage-gated Ca^ (2+) channels, contributing to the pathogenesis of persistent pain.
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