| Project/Area Number |
15K14961
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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 |
Pharmacology in pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
金子 周司 京都大学, 薬学研究科, 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)
IMAI Satoshi 京都大学, 医学部附属病院, 講師 (80468579)
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| Research Collaborator |
SO Kanako
MIYAKE Takahito
OGIHARA Takashi
TEI Yuna
HIYAMA Haruka
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | しびれ / 感覚神経 / 末梢神経障害 / オキサリプラチン / 末梢血流障害 / TRPA1 / 糖尿病性神経障害 / MrgprB4 / 薬理学 / 痛み / MRGPRB4 / TRPチャネル / 感覚鈍磨 / 神経線維 |
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| Outline of Final Research Achievements |
Dysesthesia, an unpleasant abnormal sensation, is associated with various diseases, causing problems during clinical care. However, the molecular mechanisms are largely unknown. In this study, in addition to two physiological dysesthesia animal models (oxaliplatin-induced acute peripheral neuropathy and transient hindlimb ischemia/reperfusion models), we used two pathophysiological dysesthesia animal models (diabetic neuropathy and chronic hindlimb ischemia models) and analyzed sensory fiber subtype-specific alterations. We have shown that oxaliplatin or hypoxia caused by acute/chronic hindlimb ischemia or diabetic vascular insufficiency inhibit prolyl hydroxylase activity, and induce TRPA1 sensitization expressed on C-fibers, resulting in the positive symptoms of dysesthesia. By contrast, the negative symptoms (numbness) are caused by other mechanisms. Furthermore, we analyzed the properties of MrgprB4-positive sensory neurons, which is respond to massage-like stroking.
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