Analysis of arrestin and nociceptor coupling as a mechanism for the chronic pain development
| Project/Area Number |
17K19704
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Amaya Fumimasa 京都府立医科大学, 医学(系)研究科(研究院), 教授 (60347466)
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| Co-Investigator(Kenkyū-buntansha) |
中川 貴之 京都大学, 医学研究科, 准教授 (30303845)
大橋 憲太郎 岐阜大学, 工学部, 准教授 (50332953)
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| Project Period (FY) |
2017-06-30 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | アレスチン / GRK2 / 痛覚過敏 / 一次知覚神経 |
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| Outline of Final Research Achievements |
We analyzed the expression and function of GRK2, which plays an important role in the function of Arrestin, in sensory nerves, using Western blotting and immunohistochemistry to visualize GRK2-positive neurons in dorsal root ganglia. We found that the expression of GRK2 increased during the recovery period of the postoperative pain model, and that the restored pain threshold was lowered again when GRK2 inhibitor was administered. In the postoperative pain model, we found that IGF1 synthesized in plantar tissues increased the expression of GRK2. Comprehensive phosphoproteomic analysis revealed a group of molecules that are phosphorylated by arrestin-GRK2 in the postoperative pain model.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性痛は罹患者数が多く、患者のQOLを低下させる。本研究は、アレスチン-GRK2の機能に注目し解析することで新しい慢性痛治療法を提案することを目的として行われた。
術後痛モデルにおいて急性痛が消退する時期にGRK2の発現が増加し、GRK2を阻害することで痛みが慢性化した。GRK2の発現はIGFにより制御されることが示された。このことから、GRK2の機能不全が痛みの慢性化に大きく関わる可能性が示され、アレスチン-GRK2を標的とする疼痛治療の可能性を提案することができた。また、網羅的に同定されたリン酸化タンパク群の機能解析を今後実施し、新しい疼痛治療法確立のきっかけを提案することができた。
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Report
(5 results)
Research Products
(13 results)
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[Journal Article] Prevalence of chronic postsurgical pain after thoracotomy and total knee arthroplasty: a retrospective multicenter study in Japan (Japanese Study Group of Subacute Postoperative Pain)2018
Author(s)
Yoko Sugiyama, Hiroki Iida, Fumimasa Amaya, Kanako Matsuo, Yutaka Matsuoka, Keiko Kojima, Fumitaka Matsuno, Takayuki Hamaguchi, Masako Iseki, Keisuke Yamaguchi, Yoshika Takahashi, Atsuko Hara, Yusuke Sugasawa, Mikito Kawamata, Satoshi Tanaka, Yoshimi Inagaki, Akihiro Otsuki, Mitsuaki Yamazaki, Hisakatsu Ito
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Journal Title
Journal of Anesthesia
Volume: -
Issue: 3
Pages: 434-438
DOI
Related Report
Peer Reviewed / Open Access
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