| Project/Area Number |
25670285
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pain science
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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(Renkei-kenkyūsha) |
KANEKO Shuji 京都大学, 薬学研究科, 教授 (60177516)
SHIRAKAWA Hisashi 京都大学, 薬学研究科, 准教授 (50402798)
MORI Yasuo 京都大学, 工学研究科, 教授 (80212265)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | しびれ / 疼痛 / 動物モデル / 感覚神経 / TRPA1 / オキサリプラチン / 虚血再灌流 / 低酸素 / 末梢神経障害 / 末梢血流障害 / 等津 / 活性酸素種 / 虚血/再灌流 |
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| Outline of Final Research Achievements |
Oxaliplatin, a platinum-based chemotherapeutic agent, causes an unusual acute peripheral neuropathy triggered by cold in almost all patients within hours after its infusion. We found that oxaliplatin induced rapid-onset cold hypersensitivity in mice, which may represent painful dysesthesia considering the drug sensitivity to analgesics. Furthermore, we established another mouse dysesthesia model that transient hindlimb ischemia-reperfusion evoked spontaneous licking behavior, which was accompanied with hypoesthesia against tactile stimuli. TRPA1, a polymodal nociceptor expressed on primary sensory neurons, is involved in both painful dysesthesia models. Furthermore, we found that oxalate, a metabolite of oxaliplatin, or hypoxia induced TRPA1 sensitization to reactive oxygen species by inhibition of prolyl hydroxylase-mediated hydroxylation of a N-terminal proline residue 394 in TRPA1. In this study, we elucidated the molecular mechanism underlying an aspect of painful dysesthesia.
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