Role of Substance P in Chronic Pain as a Risk Factor for Dementia
Project/Area Number |
18K08866
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55050:Anesthesiology-related
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Research Institution | Juntendo University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
長岡 功 順天堂大学, 大学院医学研究科, 教授 (60164399)
井関 雅子 順天堂大学, 医学部, 教授 (80221076)
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 高齢者 / 認知症 / サブスタンスP / 神経原性炎症 / 抗炎症作用 / 慢性疼痛 / 抑肝散 / 認知機能障害 / シグナル伝達 / マイクログリア / アストロサイト / 炎症 / デクスメデトミジン / LPS / サブスンタンスP / 認知症の行動・心理症状 / 脳内炎症 / U373MG細胞 / シグナル伝達系 / 漢方 / 行動・心理症状 |
Outline of Final Research Achievements |
Yokukansan has been shown to have an effect on neurokinin 1 receptor-mediated signal transduction for neurogenic inflammation caused by the neurotransmitter substance P (SP). In particular, among MAPKs, by suppressing the phosphorylation of P38 MAPK, the transcription factor NF-kB is suppressed in the nucleus, resulting in the production of inflammatory mediators such as IL-6, IL-8, and COX-2. It was suggested that yokukansan may improve dementia behavioral and psychological symptoms by its anti-inflammatory effect on SP.
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Academic Significance and Societal Importance of the Research Achievements |
高齢者における慢性疼痛が将来的な認知症のリスクに関連するという報告から、慢性疼痛の適切な治療が認知症発症の予防になり得るという発想に至った。慢性疼痛の多くが神経障害性疼痛に関連した難治性疼痛であり、薬物療法が治療の中心となる。高齢患者における薬物療法において、漢方薬は安全性の面からも比較的処方し易いと考えられているが、科学的根拠に基づいた研究は、これまでなかった。本研究結果から、漢方薬抑肝散は、サブスタンスPによる神経原性炎症に抗炎症的に作用することが明らかになり、慢性疼痛および認知症行動・心理症状改善のメカニズムの認知症治療法確立の足掛かりになることが期待された。
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Report
(5 results)
Research Products
(26 results)
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[Journal Article] Switching from pregabalin to mirogabalin in patients with peripheral neuropathic pain: a multi-center, prospective, single-arm, open-label study (MIROP Study).2021
Author(s)
Kimura Y, Yamaguchi S, Suzuki T, Kato J, Chiba S, Hirakawa N, Yamaguchi K, Tanabe Y, Takatsuna H, Kenyoshi Y, Shiosakai K, Sakai M, Iseki M
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Journal Title
Pain Ther
Volume: 10
Issue: 1
Pages: 711-727
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] In Vitro Analyses of Spinach-Derived Opioid Peptides, Rubiscolins: Receptor Selectivity and Intracellular Activities through G Protein- andβ-Arrestin-Mediated Pathways.2021
Author(s)
Karasawa Y, Miyano K, Fujii H, Mizuguchi T, Kuroda Y, Nonaka M, Komatsu A, Ohshima K, Yamaguchi M, Yamaguchi K, Iseki1 M, Uezono Y, Hayashida M
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Journal Title
Molecules
Volume: 26
Issue: 19
Pages: 6079-6079
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Histone modification of pain-related gene expression in spinal cord neurons under a persistent postsurgical pain-like state by electrocautery.2021
Author(s)
Katsuda Y, Tanaka K, Mori T, Narita M, Takeshima H, Kondo T, Yamabe Y, Matsufuji M, Sato D, Hamada Y, Yamaguchi K, Ushijima T, Inada E, Kuzumaki N, Iseki M, Narita M
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Journal Title
Mol Brain
Volume: 14
Issue: 1
Pages: 146-146
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of endothelin A receptor by a novel, selective receptor antagonist enhances morphine-induced analgesia: Possible functional interaction of dimerized endothelin A and μ-opioid receptors. Biomed Pharmacother.2021
Author(s)
Kuroda Y, Nonaka M, Kamikubo Y, Ogawa H, Murayama T, Kurebayashi N, Sakairi H, Miyano K, Komatsu A, Dodo T, Nakano-Ito K, Yamaguchi K, Sakurai T, Iseki M, Hayashida M, Uezono Y
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Journal Title
Biomed Pharmacother.
Volume: 141
Pages: 111800-111800
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Insomnia and caregiver burden in chronic pain patients: A cross-sectional clinical study.2020
Author(s)
M Yamaguch, K Yamada, M Iseki, Y Karasawa, Y Murakam, T Enomoto, N Kikuchi, S Chiba, A Hara, K Yamaguch, E Inada
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Journal Title
PLoS One
Volume: 15(4)
Issue: 4
Pages: e0230933-e0230933
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 胸髄損傷後慢性疼痛に対し、脊髄刺激療法を導入した1例2020
Author(s)
石橋 千佳, 飯田 史絵, 前田 剛, 齋藤 貴幸, 田中 英文, 中村 かんな, 秋山 絢子, 今井 美奈, 萬代 秀樹, 高倉 朋和, 山口 敬介
Organizer
第40回日本疼痛学会
Related Report
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