| Project/Area Number |
21600009
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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 |
疼痛学
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| Research Institution | National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East |
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Principal Investigator |
UEZONO Yasuhito 独立行政法人国立がん研究センター, 研究所, 分野長 (20213340)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | GABA_B受容体 / μ受容体 / 耐性 / オピオイド / FRET / β-アレスチン / ケタミン / 受容体陥入 / GABAB receptor / Xenopus oocyte / Tolerance / Opioids / β-arrestin / ketamine / receptor internalization / 脱感作 / 緩和医療 / バクロフェン / モルヒネ / 髄腔内投与法 / オピオイド受容体 / 難治性疼痛 |
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| Research Abstract |
Management of refractory pain seen in advanced cancer patients is hard to control, and in such cases intrathecal morphine(ITM) or intrathecal baclofen treatment(ITB) is currently used. However, persistent use of either ITM or ITB often causes tolerance due to desensitization ofμ-opioid(μOR) or GABA_B receptors(GBR).
To overcome such issue, we demonstrated by using in vitro experimental system that 1) treatment of baclofen with ketamine suppressed GBR desensitization, 2) GBR did not internalize because of failure of association withβ-arrestins, key proteins for receptor desensitization, 3) in cells coexpressingμOR and GBR, combination of low concentrations of morphine and baclofen hardly caused receptor desensitization. These results suggest that some of newer treatments described above would be useful for the control of refractory pain by prevention of receptor desensitization.
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