| Project/Area Number |
26460101
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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 |
Pharmacology in pharmacy
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
TAN-NO Koichi 東北医科薬科大学, 薬学部, 教授 (20207260)
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| Co-Investigator(Kenkyū-buntansha) |
中川西 修 東北医科薬科大学, 薬学部, 准教授 (50296018)
根本 亙 東北医科薬科大学, 薬学部, 助手 (80635136)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 慢性疼痛 / １型糖尿病 / 糖尿病性神経障害性疼痛 / アンジオテンシンⅡ / アンジオテンシン変換酵素 / AT1受容体 / ロサルタン / p38 MAPK / 1型糖尿病 / アンジオテンシンII / 抗アロディニア作用 / マウス |
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| Outline of Final Research Achievements |
Tactile allodynia was observed concurrently with an increase in blood glucose levels the day after mice received streptozotocin (STZ) injection. Tactile allodynia on day 14 was dose-dependently inhibited by intrathecal administration of losartan, an AT1 receptor antagonist. In the lumbar dorsal spinal cord, the expression of angiotensin (Ang) II, Ang converting enzyme (ACE) and phospho-p38 MAPK were all significantly increased on day 14 after STZ injection compared with vehicle-treated controls, whereas no differences were observed among AT1 receptors or angiotensinogen levels. Moreover, the increase in phospho-p38 MAPK was significantly inhibited by intrathecal administration of losartan. These results indicate that the expression of spinal ACE increased in STZ-induced diabetic mice, which in turn led to an increase in Ang II levels and tactile allodynia. This increase in spinal Ang II was accompanied by the phosphorylation of p38 MAPK, which was shown to be mediated by AT1 receptors.
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