| Project/Area Number |
18K17702
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 59010:Rehabilitation science-related
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| Research Institution | Nishikyushu University |
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Principal Investigator |
Kishikawa Yuki 西九州大学, リハビリテーション学部, 講師 (30783360)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 慢性疼痛 / 痛覚閾値低下 / 関節不動化 / ドパミン / 側坐核 / ドパミンD2受容体 / カッパーオピオイド受容体 / 中脳辺縁系 / 不動化 / 慢性痛 / 痛覚閾値 / 報酬系 / 神経科学 / 情動 |
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| Outline of Final Research Achievements |
The present study demonstrated that mechanical hypersensitivity induced by chronic cast immobilization was attributable to altered dopaminergic neurotransmission in the nucleus accumbens (NAc). In vivo microdialysis combined with drug infusion into the NAc revealed that D2 receptor blockade in the NAc reversed mechanical hypersensitivity, whereas D2 receptor activation in the NAc mimicked mechanical hypersensitivity despite normal or low dopamine levels, suggesting that mechanical hypersensitivity is presumably mediated through upregulation of postsynaptic D2 receptors in the NAc. This interpretation is supported by the increase of Drd2 mRNA in the NAc. In addition, mechanical stimulation of the cast-immobilized hind limb induced the decrease of dopamine in the NAc due to upregulation of presynaptic D2 receptors at dopaminergic terminals.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性的な痛みは、急性疼痛の組織損傷を伴う痛みとは異なり、ストレスや抑うつ状態などの心理的要因が痛みの認知に大きく関与する。そこで、情動の変化に関係する中脳辺縁系ドパミン神経に焦点を当て、慢性疼痛に対する新規治療の糸口を得たいと考えた。結果として、ドパミンD2受容体拮抗薬を投与すると痛覚閾値が上昇した。したがって、ドパミンD2受容体拮抗薬は慢性疼痛の治療薬となる可能性が示唆された。
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