Functional analysis in anterior cingulate cortex and development of therapeutic agent using P2X7 receptor sequences on fibromyalgia
| Project/Area Number |
17K09050
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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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| Research Field |
Pain science
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| Research Institution | Fukuoka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松本 太一 福岡大学, 薬学部, 助教 (80570803)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 線維筋痛症 / 疼痛 / 前頭前野 / 帯状回 / ムスカリンM1受容体 / GABAB受容体 / ストレスモデルマウス / 前辺縁皮質 / c-fos / 前帯状回 / P2X7受容体 |
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| Outline of Final Research Achievements |
We investigated the mechanism of neuropathic pain in the brain of fibromyalgia. To investigate pain assessment and c-fos protein expression, we made mouse models for fibromyalgia, including of RCS (repeated cold stress), SS (social stress), UGIAS (unilateral gastrocnemius injection with acidic saline) and PSNL (partial sciatic nerve ligation) models. All mouse models showed the hypersensitivity to the mechanical stimulation using von Frey filament. In SS and RCS mice, c-fos protein was expressed in prefrontal cortex. On the other hand, PNSL-induced mechanical hypersensitivity was inhibited by an intracerebroventricular administration of a muscarinic M1 receptor agonist. Further, the muscarinic M1 agonist-induced alleviative effect was inhibited by a GABAB receptor antagonist.
These results suggest that the pain in fibromyalgia may be alleviated by a muscarinic M1 receptor agonist and a GABAB receptor agonist.
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| Academic Significance and Societal Importance of the Research Achievements |
線維筋痛症の患者は、日本だけでも200万人はいると推定されており、発症原因は明らかにされていない。また、有効な治療薬がほとんどないため、多くの方が症状の疲労感や疼痛で苦しんでいる。本研究では、慢性疼痛に対して脳内のムスカリンM1受容体アゴニストがGABAB受容体を介して抑制効果があることを示した。今後、中枢性のムスカリンM1受容体アゴニストやGABAB受容体アゴニストを開発することで、線維筋痛症の新たな治療薬を創出できることが期待でき、本研究は学術的および社会的に意義深い。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Stimulating muscarinic M1 receptors in the anterior cingulate cortex reduces mechanical hypersensitivity via GABAergic transmission in nerve injury rats2019
Author(s)
Koga K, Matsuzaki Y, Migita K, Shimoyama S, Eto F, Nakagawa T, Matsumoto T, Terada K, Mishima K, Furue H, Honda K
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Journal Title
Brain Res
Volume: 1704
Pages: 187-195
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Propofol anesthesia is reduced in Phospholipase C-related inactive protein type-1 knockout mice2017
Author(s)
Nikaido Y, Furukawa T, Shimoyama S, Yamada J, Migita K, Koga K, Kushikata T, Hirota K, Kanematsu T, Hirata M, Ueno S
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Journal Title
The Journal of pharmacology and experimental therapeutics
Volume: 361(3)
Issue: 3
Pages: 367-374
DOI
Related Report
Peer Reviewed / Open Access
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