The underlying mechanism of glucocorticoid-regulated diurnal exacerbation of neuropathic pain hypersensitivity and its evaluation as a target of anti-allodynic drug
Project/Area Number |
15H04765
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pain science
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Research Institution | Kyushu University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
TSUDA Makoto 九州大学, 薬学研究院, 教授 (40373394)
MATSUNAGA Naoya 九州大学, 薬学研究院, 助教 (10432915)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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Keywords | 副腎皮質ホルモン / 概日リズム / 神経障害痛 |
Outline of Final Research Achievements |
Neuropathic pain hypersensitivity is often caused by peripheral nerve injury, which is refractory to contemporary analgesic treatment. Diurnal exacerbation in pain hypersensitivity are common in the patients with nerve injury, but the underlying mechanisms are enigmatic. In this study, we found that diurnal exacerbation of pain hypersensitivity is mediated by glucocorticoid (GC)-induced enhancement of the extracellular release of ATP in the spinal cord, which stimulates purinergic receptors on microglia in the dorsal horn. GC-regulatory factor (SGK-1) was the key molecule responsible for the GC-enhanced release of ATP from astrocytes. Using high-throughput screening system, we identified candidate as an anti-analgesic drug that has the ability to inhibit SGK-1 activity. Now novel therapeutic approaches are facilitated by development of synthetic ligands targeted to the key molecule that causing diurnal exacerbation of pathological events.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia.2016
Author(s)
S. Koyanagi, N. Kusunose, M. Taniguchi, T. Akamine, Y. Kanado, Y. Ozono, T. Masuda, Y. Kohro, N. Matsunaga, M. Tsuda, M. Salter, K. Inoue, and S. Ohdo.
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Journal Title
Nat. Commun.
Volume: 7
Issue: 1
Pages: 13102-13102
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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