2022 Fiscal Year Final Research Report
Modulation of pain perception by energy metabolism
| Project/Area Number |
20K07770
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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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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Hyogo Medical University (2022)
Hyogo University of Health Sciences (2020-2021) |
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Principal Investigator |
Dai Yi 兵庫医科大学, 医学部, 教授 (20330441)
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| Co-Investigator(Kenkyū-buntansha) |
神田 浩里 兵庫医科大学, 薬学部, 助教 (80842088)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 糖尿病性ニューロパシー / TRPA1 / AMPK / Nedd4-2 / ユビキチンリガーゼ |
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| Outline of Final Research Achievements |
In the study, by focusing on the interaction between pain and AMP-activated protein kinase (AMPK), a cell energy sensor in the metabolic disease, we investigate the molecular mechanisms of how cell energy disorder contributes the sensory disfunction. The following achievements were reached. 1) we have successfully established metabolic disordered animal models which accompanied with hypersensation. 2) We demonstrated a functional link between AMPK-Nedd4-2 signaling and TRPA1 channels, in which AMPK negatively regulates TRPA1 in dorsal root ganglion neurons through the Nedd4-2-mediated ubiquitination of TRPA1. This ubiquitination leads downregulating TRPA1 plasma membrane expression. This results could represent an underlying mechanism and potential therapeutic molecular target in painful diabetic neuropathy. 3) we have identified several genes which are involved in the diabetic neuropathy, giving the molecule candidates for further elucidating its pathophysiology.
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| Free Research Field |
疼痛研究
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| Academic Significance and Societal Importance of the Research Achievements |
生体のエネルギー代謝異常は肥満や糖尿病をはじめ、様々な病気をもたらす。本研究はエネルギー代謝異常の感覚受容にもたらす影響とその分子機序を探求した。得られた研究成果はAMPK-Nedd4-2シグナルによる疼痛受容体タンパクの調節が疼痛過敏の発症に寄与することが示唆された。
本研究成果は、先行臨床研究で示されたAMPK活性化薬剤の鎮痛効果の薬理機序を解明し、今後こうした薬剤を鎮痛薬として活用される科学的根拠を提供した。特に、II型糖尿病患者の治療に使われるmetformin(メトフォルミン)は、糖尿病性ニューロパシーへの積極的に使用すべきことが示唆された。
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