Analysis to reveal the roles of TREK1 on cancer pain and to develop TREK1 agonists as novel analgesics for cancer patients
| Project/Area Number |
16K08568
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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 |
General pharmacology
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Miyano Kanako 国立研究開発法人国立がん研究センター, 研究所, 研究員 (50597888)
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| Co-Investigator(Kenkyū-buntansha) |
上園 保仁 国立研究開発法人国立がん研究センター, 研究所, 分野長 (20213340)
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| Project Period (FY) |
2016-04-01 – 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 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | TREK1チャネル / オピオイド受容体 / TRPチャネル / 疼痛 / TREK1 / 神経科学 / 薬理学 |
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| Outline of Final Research Achievements |
The aim of the present study was to reveal the roles of TREK1 on cancer pain and to develop TREK1 agonists as novel analgesics for cancer patients. We first constructed cells stably expressing opioid receptors (ORs), which were reported to activate TREK1. We next established cells expressing TREK1 and cells simultaneously expressing TREK1 and μOR. We then investigated effects of opioid analgesics on TREK1 activation and performed screenings of novel TREK1 using these cells.
In the mean time, we established a novel chemotherapy-induced neuropathic pain (CINP) mouse model using carboplatin, which showed enhanced TRPA1 activation via cAMP-PKA-AKAP pathway and induced mechanical and cold allodynia. Using this CINP model, investigation of involvement of TREK1 activities on neuropathic pain are ongoing.
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| Academic Significance and Societal Importance of the Research Achievements |
TREK1活性化剤は、TREK1を介した細胞内外のイオンバランス調整により疼痛および鎮痛の両面での神経活性を制御し、結果として鎮痛作用を発揮させるため、既存の鎮痛薬に比較し有効かつ副作用や耐性の生じにくい鎮痛薬となり得る。本研究は、難治性疼痛の克服によりがん患者のがん治療の継続を可能にすることで治療の完遂を促し、患者のQOL向上に寄与するだけでなく患者の生命予後の延長にも貢献すると考える。
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Report
(5 results)
Research Products
(50 results)
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[Journal Article] Neuropeptide oxytocin enhances μ opioid receptor signaling as a positive allosteric modulator.2018
Author(s)
Meguro, Y., Miyano, K., Hirayama, S., Yoshida, Y., Ishibashi, N., Ogino, T., Fujii, Y., Manabe, S., Eto, M., Nonaka, M., Fujii, H., Ueta, Y., Narita, M., Sata, N., Yada, T., Uezono, Y.
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Journal Title
J Pharmacol Sci
Volume: 137
Issue: 1
Pages: 67-75
DOI
Related Report
Peer Reviewed
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[Journal Article] Usefulness for the combination of G-protein- and β-arrestin-biased ligands of μ-opioid receptors: Prevention of antinociceptive tolerance2017
Author(s)
Tomohisa Mori, Naoko Kuzumaki, Takamichi Arima, Michiko Narita, Ryunosuke Tateishi, Takashige Kondo, Yusuke Hamada, Hirotsugu Kuwata, Miho Kawata, Mitsuaki Yamazaki, Kazuyuki Sugita, Akinobu Matsuzawa, Kanae Baba, Takayasu Yamauchi, Kimio Higashiyama, Miki Nonaka, Kanako Miyano, Yasuhito Uezono, Minoru Narita
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Journal Title
Molecular Pain
Volume: 13
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Ignavine: a novel allosteric modulator of the μ opioid receptor.2016
Author(s)
Ohbuchi K, Miyagi C, Suzuki Y, Mizuhara Y, Mizuno K, Omiya Y, Yamamoto M, Warabi E, Sudo Y, Yokoyama A, Miyano K, Hirokawa T, Uezono Y.
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 31748-31748
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Characterization of the properties of four opioid analgesics approved in Japan with cells stably expressing µORs using the CellKeyTM and GloSensorTM cAMP assay systems.2018
Author(s)
Manabe, S., Miyano, K., Ogino, T., Ohshima, K., Uzu, M., Nonaka, M., Matsuoka, Y., Sato, T., Morimatsu, H., Uezono, Y.
Organizer
18th World Congress of Basic and Clinical Pharmacology
Related Report
Int'l Joint Research
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[Presentation] Molecular characterization and comparison of the effects of several opioid agonists clinically used in Japan - Using the CellKeyTM and internalization assays with stable cells expressing opioid µ, δ or µ/δ dimerized receptors.2018
Author(s)
Fujii, Y., Miyano, K., Oshima, K., Manabe, S., Someya, R., Yoshizawa, K., Morimatsu, H., Iseki, M., Inada, E., Uezono, Y.
Organizer
18th World Congress of Basic and Clinical Pharmacology
Related Report
Int'l Joint Research
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[Presentation] Oxytocin involvement of μ-opioid receptor-mediated analgesia and relationship between functions of oxytocin and kamikihito, a Japanese kampo medicine.2017
Author(s)
Uezono, Y., Meguro, Y., Miyano, K., Hirayama, S., Ogino, T., Ishibashi, N., Yoshida, Y., Fujii, H., Higami, Y.
Organizer
International Society for Autonomic Neuroscience 2017
Related Report
Int'l Joint Research
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