Research on the analgesic mechanism induced by the stimulation of the new free fatty acid receptor GPR40.
Project/Area Number |
25462225
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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 |
Research Field |
Neurosurgery
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Research Institution | Kagoshima University |
Principal Investigator |
Oyoshi Tatsuki 鹿児島大学, 医歯学域医学部・歯学部附属病院, 講師 (80315407)
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Co-Investigator(Kenkyū-buntansha) |
Arita Kazunori 鹿児島大学, 医歯学域医学系, 教授 (90212646)
Miyata Atsuro 鹿児島大学, 医歯学域医学系, 教授 (60183969)
Kurihara Takashi 鹿児島大学, 医歯学域医学系, 准教授 (60282745)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 遊離脂肪酸受容体 / GPR40 / 神経障害性疼痛 / 炎症性疼痛 / 脊髄 / 後根神経節 / ホールセルパッチクランプ / FFAR1 / GPR40/FFAR1遺伝子欠損マウス / 情動行動 / 脳内モノアミン系 / 遊離脂肪酸 |
Outline of Final Research Achievements |
The functional role of the G-protein-coupled receptor 40 (GPR40) in nervous system including somatosensory pain signaling has not been fully examined yet. Intrathecal injection of GPR40 agonist (MEDICA16 or GW9508) dose-dependently reduced ipsilateral mechanical allodynia and thermal hyperalgesia in several inflammatory and peripheral neuropathic pain models. Immunohistochemical analysis revealed that GPR40 is expressed in spinal dorsal horn and dorsal root ganglion neurons, and immunoblot analysis showed that peripheral inflammation or nerve injury resulted in increased expression of GPR40 in these areas. Patch-clamp recordings exhibited that bath-application of either MEDICA16 or GW9508 significantly decreased the frequency of spontaneous excitatory postsynaptic currents in the substantia gelatinosa neurons of the pain models. Our results indicate that GPR40 agonists might serve as a new class of analgesics for treating inflammatory and neuropathic pain.
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Report
(3 results)
Research Products
(34 results)
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[Journal Article] Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation.2013
Author(s)
Miura, A., Kambe, Y., Inoue, K., Tatsukawa, H., Kurihara, T., Griffin, M., Kojima, S. & Miyata, A.
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Journal Title
Journal of Biological Chemistry
Volume: 288
Issue: 45
Pages: 32720-32730
DOI
Related Report
Peer Reviewed
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[Presentation] Spinal PACAP-PAC1 signaling induces long-lasting mechanical allodynia by astroglial activation.2015
Author(s)
Miyata, A, Yokai, M., Onou, T., Kambe Y., Takasaki I., Kurihara, T
Organizer
12th international symposium on VIP/PACAP and related peptides
Place of Presentation
Cappadocia, Turkey
Year and Date
2015-09-21
Related Report
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