| Project/Area Number |
16K10813
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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 |
Orthopaedic surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ENOMOTO Mitsuhiro 東京医科歯科大学, 医学部附属病院, 非常勤講師 (90451971)
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| Co-Investigator(Kenkyū-buntansha) |
早乙女 進一 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (20401391)
大川 淳 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30251507)
辻 邦和 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (20323694)
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| Research Collaborator |
YOKOYAMA Hiroyuki
HIRAI Takashi
LI Leyang
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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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 慢性疼痛 / 末梢神経損傷 |
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| Outline of Final Research Achievements |
We established three different types of mouse neuropathic pain models and compared their behavioral changes to expressions of Ca channel α2δ-1 subunit (α2δ-1) among them. The higher expressions of α2δ-1 in lumbar DRGs of all models were observed than the non-injury model. However, the patterns of hypersensitivities were not correlated to the α2δ-1 expressions at chronic phase after injury. We should investigate pain molecules commonly expressing in all pain models. Meanwhile, DRGs from mice with spared nerve injury were analyzed with DNA microarray. Arginine vasopressin receptor was found to be highly expressed in the DRGs 3 weeks after injury. The receptor would be expressing in the DRG glia and a therapeutic target for neuropathic pain. DRGs could divide into neurons and glias by using flow cytometry. We will elucidate functions of the receptor and develop therapeutics with DNA/RNA heteroduplex oligonucleotide in the near future.
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| Academic Significance and Societal Importance of the Research Achievements |
神経障害性疼痛治療薬プレガバリンの標的分子Caチャネルα2δサブユニットの発現パターンは、マウス神経障害性疼痛モデルの感覚障害と相関しないことが明らかとなった。臨床的にプレガバリンに反応しない症例も多く、新規疼痛分子探索の必要性が示唆された。本研究で同定したバソプレッシン関連分子はグリアや血管内皮にも作用し、新規標的分子として有望である。ただし、疼痛に関連する具体的な作用機序は明らかではなく、今後、DRGをニューロン、グリア、血管等に分けて解析する必要がある。本学で開発されたヘテロ2本鎖核酸を利用した遺伝子発現制御がDRGで可能になれば、難治性疼痛の新たな治療法として期待できる。
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