Brain-Spinal Cord Plasticity Changes during the Establishment of Chronic Pain: Elucidation of the Role of Inhibitory Neural Circuits
| Project/Area Number |
18K08811
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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 55050:Anesthesiology-related
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐々木 美佳 新潟大学, 医歯学系, 助教 (20774061)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 青斑核 / in vivoパッチクランプ / 化学遺伝学的手法 / 薬理遺伝学的手法 / 慢性痛 / 脊髄後角 / 可塑性変化 / in vivo patch clamp / 脊髄可塑性 |
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| Outline of Final Research Achievements |
We hypothesized that not only hyperexcitability of excitatory neurotransmission but also hyperexcitability of inhibitory neuronal circuits may be involved in the synaptic plasticity changes that develop during the establishment of chronic pain. We aimed to elucidate the role of inhibitory circuits in spinal plasticity from the early stage of peripheral nerve injury to the establishment of chronic pain, focusing especially on the descending inhibitory system.
Using the DREADD system, we selectively activated neurons in locus coeruleus, one of the originating nuclei of the descending inhibitory system, and analyzed their effects on pain responses. In addition to the in vivo patch-clamp method, behavioral and immunohistological analyses were also performed to conduct an integrated study to elucidate the role of the descending inhibitory system in pain.
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| Academic Significance and Societal Importance of the Research Achievements |
神経障害後からの経時的な脊髄後角抑制性シナプス電流の解析を初めて行った。その結果、神経障害後の経過とともに変化し、最終的に慢性痛時にはGABAあるいはGlycineの受容体の感受性変化により応答が減弱していることを示した。一方で、化学遺伝学的手法を用いて下降性抑制系の起始核の一つである青斑核NAニューロンを操作したところ急性痛に対してNAニューロンの活性化は鎮痛作用を示した。神経障害後からのシナプス可塑性変化が従来の慢性痛治療が難渋する理由の一つである可能性が示唆された。
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Report
(4 results)
Research Products
(7 results)
