2023 Fiscal Year Final Research Report
Study on pain modulation by the interaction of coagulation factors with HMGB1 and its clinical relevance
| Project/Area Number |
21K06608
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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 47040:Pharmacology-related
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| Research Institution | Kindai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
関口 富美子 近畿大学, 薬学部, 准教授 (90271410)
坪田 真帆 近畿大学, 薬学部, 講師 (90510123)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 痛み / 化学療法誘発性末梢神経障害 / トロンボモジュリン / 内臓痛 / 抗凝固薬 / トロンビン / 結腸過敏 / 糖尿病性末梢神経障害 |
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| Outline of Final Research Achievements |
We have previously reported that intractable pain including chemotherapy-induced peripheral neuropathy (CIPN) involves extracellular release of nuclear HMGB1, and that endothelial thrombomodulin (TM) prevents CIPN by inactivating HMGB1 in a thrombin (TB)-dependent manner. We thus tested the hypothesis that inhibition of TB activity or production might aggravate intractable pain. Our data demonstrated that anticoagulants cancelled the preventive effect of soluble TM on CIPN, butyrate-induced colonic hypersensitivity (BICH) and diabetic peripheral neuropathy, and also aggravated CIPN and BICH. Moreover, our clinical data analyses ascertained the aggravation of CIPN by anticoagulants in humans. Thus, our study unveiled the pain modulation by the blood coagulation system.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題の遂行により、多様な難治性疼痛の発症に核内タンパクHMGB1が関与すること、HMGB1を不活性化するトロンボモジュリン／トロンビン(TB)系が痛みを抑制的に制御していることを再確認し、TBの活性・産生を抑制する抗凝固薬が各種難治性疼痛を増悪させることを明らかにすることができた。今回検証した「血液凝固系による痛み制御」は、これまでにない新しい概念であり、「抗凝固薬による痛み増悪」は臨床的に極めて重要な新知見で、社会的意義は極めて大きいと考える。
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