Identification of pain-specific nerve growth factor signaling and development of mechanism-based novel therapeutics for chronic pain
| Project/Area Number |
17K18093
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pain science
Anesthesiology
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| Research Institution | Keio University |
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Principal Investigator |
KATO Jungo 慶應義塾大学, 医学部(信濃町), 助教 (40465018)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 慢性痛 / 神経成長因子 / 関節炎 / 先天性無痛無汗症 / 鎮痛薬 / 骨破壊 / 痛み / 術後痛 / 神経障害性疼痛 / 炎症性疼痛 / 痛覚神経活性化マーカー / 精製タンパク / 後根神経節 in vitro assay / ウェスタンブロット / 痛覚感作 |
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| Outline of Final Research Achievements |
Chronic pain remains a huge socio-economical problem affecting millions of citizens. We have focused on nerve growth factor (NGF) signaling to identify novel therapeutic targets against chronic pain. In this project, we established a transgenic mouse line that modeled hereditary sensory and autonomic neuropathy type V (HSAN V), in which the NGF mutation results in bone/joint-specific painless phenotype. We observed painless phenotype in the NGF-mutated mice specifically when inflammation takes place in their joints. On the other hand, we found that the maturation and secretion of NGF in salivary gland were normal. The immunohistochemical analysis revealed that the development of pain-related nerve system remained normal in the NGF-mutated mice. Moreover, the bone erosion caused by joint inflammation was significantly attenuated in the NGF-mutated mice. Taken together, the altered NGF signaling taking place in the NGF-mutated mice can be a novel analgesic target for chronic pain.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性疼痛は様々な病因で発症し、実に25%にあたる多くの国民に苦痛、QOLの著しい低下をもたらし、社会生活活動の低下から大きな社会問題を招いている。従来の治療では満足が得られないことが多く、発症機序のさらなる理解とそれに基づく新規治療法の確立が喫緊の課題である。NGFは古くから鎮痛標的として注目を集めてきたが、副作用の問題から臨床応用へは至っておらず、より痛みに特異的なシグナリングの同定が求められてきた。本研究のNGF変異マウスでのシグナリングは骨保護作用を有する鎮痛効果が期待でき、創薬への発展が期待される。
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Report
(4 results)
Research Products
(8 results)
