Roles of ROS-sensitive TRP channels in generation and prolongation of pain and dysesthesia
| Project/Area Number |
26293019
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
Nakagawa Takayuki 京都大学, 医学(系)研究科(研究院), 准教授 (30303845)
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| Co-Investigator(Kenkyū-buntansha) |
金子 周司 京都大学, 薬学研究科(研究院), 教授 (60177516)
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| Co-Investigator(Renkei-kenkyūsha) |
SHIRAKAWA Hisashi 京都大学, 大学院薬学研究科, 准教授 (50402798)
MORI Yasuo 京都大学, 大学院工学研究科, 教授 (80212265)
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| Research Collaborator |
SO Kanako
DOGISHI Koji
ISAMI Koichi
MIYAKE Takahito
KODERA Mizuki
OYAMA Shohei
SUKEISHI Asami
TEI Yuna
HIYAMA Haruka
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2014: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | TRPチャネル / 活性酸素種 / 痛み / しびれ / オキサリプラチン / TRPA1 / TRPM2 / 慢性膀胱炎 / 薬理学 / 感覚神経 / 末梢神経障害 / 末梢血流障害 / 疼痛 / グリア細胞 / 抗がん剤誘発末梢神経障害 / シュワン細胞 / ミクログリア / 抗がん剤末梢神経障害 |
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| Outline of Final Research Achievements |
It is well known that reactive oxygen species (ROS) nonspecifically impairs sensory neurons, which generate unpleasant abnormal sensation, such as pain and dysesthesia. However, recent evidence suggest ROS can act on specific targets to induce physiological and pathological responses. In this study, we have shown that ROS-mediated activation of some ROS-sensitive TRP channels specifically contribute to the generation and prolongation of pain and dysesthesia. 1) TRPM2 mainly expressed on peripheral immune cells and spinal glial cells causes a wide range of pain mouse models, including inflammatory and neuropathic pain. 2) ROS-mediated activation of TRPA1, expressed on sensory neurons contributes to oxaliplatin-induced acute peripheral neuropathy and transient hindlimb ischemia/reperfusion-induced spontaneous dysesthesia, which are based to the inhibition of prolyl hydroxylase. 3) TRPA1 is involved in long-lasting cystitis model induced by intravesical injection of H2O2.
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Report
(4 results)
Research Products
(99 results)
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[Journal Article] A rat long-lasting cystitis model induced by intravesical injection of hydrogen peroxide.2017
Author(s)
Dogishi K, Okamoto K, Majima T, Konishi-Shiotsu S, Homan T, Kodera M, Oyama S, Oyama T, Shirakawa H, Yoshimura N, Nakagawa T, Kaneko S.
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Journal Title
Physiol Rep.
Volume: 5
Issue: 4
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Cold sensitivity of TRPA1 is unveiled by the prolyl hydroxylation blockade-induced sensitization to ROS.2016
Author(s)
Miyake T, Nakamura S, Zhao M, So K, Inoue K, Numata T, Takahashi N, Shirakawa H, Mori Y, Nakagawa T, Kaneko S
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Journal Title
Nature Communications
Volume: 7
Issue: 1
Pages: 12840-12840
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Hypoxia-induced sensitization of TRPA1 in painful dysesthesia evoked by transient hindlimb ischemia/reperfusion in mice2016
Author(s)
So K, Tei Y, Zhao M, Miyake T, Hiyama H, Shirakawa H, Imai S, Mori Y, Nakagawa T, Matsubara K, Kaneko S
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 23261-23261
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Hypoxia-induced sensitization of TRPA1 to reactive oxygen species causes painful dysesthesia evoked by transient hindlimb ischemia/reperfusion in mice2016
Author(s)
Nakagawa T, So K, Tei Y, Zhao M, Miyake T, Hiyama H, Shirakawa H, Imai S, Matsubara K, Mori Y, Kaneko S
Organizer
16th World Congress on Pain
Place of Presentation
横浜市
Year and Date
2016-09-26
Related Report
Int'l Joint Research
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[Presentation] The effects of frozen glove and sock on paclitaxel-induced peripheral neuropathy among breast cancer patients: matched case-control study: a self controlled clinical trial2016
Author(s)
Hanai A, Ishiguro H, Sozu T, Tsuda M, Nakagawa T, Imai S, Hamabe Y, Toi M, Arai H, Tsuboyama T
Organizer
ASCO Annual Meeting 2016
Place of Presentation
Chicago, USA
Year and Date
2016-07-03
Related Report
Int'l Joint Research
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