| Project/Area Number |
16K10988
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Anesthesiology
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| Research Institution | Kobe Gakuin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中本 賀寿夫 神戸学院大学, 薬学部, 講師 (30432636)
原田 慎一 神戸学院大学, 薬学部, 助教 (60633443)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 脳卒中後疼痛 / HMGB1 / 脳虚血 / RAGE / NOS / グリア細胞 / TLR4 / 疼痛 / 脳神経疾患 / 神経科学 / 薬理学 |
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| Outline of Final Research Achievements |
In this study, we investigated whether the interaction between spinal glial cells and HMGB1 signaling is directly involved in the induction of CPSP. Spinal HMGB1 expression increased on day 3 after bilateral carotid artery occlusion (BCAO). Intrathecal (i.t.) injection of LPS-RS and LMWH significantly blocked mechanical allodynia on day 3 after BCAO. BCAO-induced activation of spinal microglia and astrocyte were suppressed by i.t. anti-HMGB1 monoclonal antibody (mAb) and LPS-RS administration. In addition, i.t. injection of a nonselective nitric oxide synthetase (NOS) inhibitor significantly blocked mechanical allodynia on day 3 after BCAO and i.t. administration of anti-HMGB1 mAb, LPS-RS, and LMWH significantly inhibited the increase of NOS activity in the spinal cord on day 3 after BCAO. These results showed that the interaction between spinal glial cells and HMGB1/TLR4/NOS or HMGB1/RAGE/NOS is directly involved in the induction of CPSP.
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| Academic Significance and Societal Importance of the Research Achievements |
脳卒中後疼痛は、脳卒中後の難治性合併症であり、神経障害性疼痛の一つとして知られるが、現在それに対する有益な薬物療法は確立されていない。本研究成果から、BCAO 後に生じる機械的アロディニアの発症機構に、脊髄 HMGB1 の増加が関与していることを明らかにした。脳虚血領域ではない脊髄レベルにおいて、このような変化が生じ疼痛の惹起に関与しているとの研究成果は、脳卒中後疼痛の新たな治療戦略の一助となることが期待される。
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