| Project/Area Number |
21H02816
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Jikei University School of Medicine |
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Principal Investigator |
Kato Fusao 東京慈恵会医科大学, 医学部, 教授 (20169519)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2023: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2022: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2021: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 慢性痛 / 炎症 / 中枢性感作 / 腕傍核 / 扁桃体中心核 / FosTRAP / 痛覚変調性疼痛 / オピオイド受容体 / 内因性オピオイド / 光遺伝学 / CGRP / Muオピオイド受容体 / lipopolysaccharide / 痛み / 扁桃体 / FosTRAPマウス / 広汎性痛覚過敏 / 化学遺伝学 |
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| Outline of Research at the Start |
組織損傷や感染にともなう炎症は，局所的炎症応答を介して侵害受容神経を活性化させるが，炎症部位とは離れた広汎な部位に異所性の痛覚過敏を生じさせる．本研究では，炎症が，どのような機構で，痛み，それも全身の離れた部位に広がる広汎性の痛みを生じさせるのかを解明する．全身からの侵害受容情報を受け取るとともに，中枢性感作の中核機構としても機能する腕傍核ー扁桃体中心核系が，炎症によって強く活性化する事実を申請者らは見出しており，侵害受容情報と炎症情報が，腕傍核－扁桃体系を活性化してその可塑的変化を促すことにより，痛みの増強や異所性痛覚過敏などの中枢性感作を伴う慢性痛状態への移行を促す可能性を検証する．
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| Outline of Final Research Achievements |
We found that 1) brief local inflammation activates and causes plastic changes in the parabrachial-central amygdala system, 2) these plastic changes lead to nociplastic pain and result in long-lasting widespread hyperalgesia, 3) opioids markedly inhibit excitatory synaptic transmission between neurons in the parabrachial-central nucleus of the amygdala through presynaptic mechanisms. This might be a primary target of opioids for its analgesic effects and may also be a mechanism for preventing delayed chronic pain. 4) In the early phase of systemic inflammation, PBN-CeA synaptic transmission inhibition by endogenous opioids occurs, potentially suppressing hyperalgesia. The inflammatory activation accompanying nociception would determine the subsequent establishment of widespread chronic sensitization through activating the LPB-CeC system.
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| Academic Significance and Societal Importance of the Research Achievements |
侵害受容器の活性化とともに生じる炎症系の活性化は，腕傍核－扁桃体系の活性化を通じて，その後の慢性的な痛覚過敏の成立の鍵を握ることを明らかにした．今後の慢性痛予防と治療医大きな影響と示唆をもたらす研究成果である．
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