| Project/Area Number |
11671495
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Osaka University |
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Principal Investigator |
UCHIDA Ichiro Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 講師 (00232843)
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| Co-Investigator(Kenkyū-buntansha) |
TAKENOSHITA Makoto Department of Anesthesiology Siga University of Medical Sience, 医学部, 助教授 (00144486)
MASHIMO Takashi Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (60157188)
YOSHIYA Ikuo Osaka University Hospital, professor, 医学部・付属病院, 教授 (80028505)
SHIBATA Masahiko Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50216016)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Chronic pain / Na channel / Local anesthetic / Electrophysiology / Molecular pharmacology / Gene therapy / ナトリウムチャンネル |
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| Research Abstract |
The aim of this project was to explore the role of SNS Na channel in the mechanism of chronic pain (neuropathic pain). However the expression of SNS Na+ channel in the oocyte system has not been achieved to the level to collect the data for the assessment using the electrophysiological method. Therefore we have focused on the NMDA receptors and 5-HT3 receptor in the central nervous system as one of target receptors involved in the mechanism of chronic pain,. First, we examined the interactions of NMDA receptor and the neuropathic agents such as local anesthetics, using the recombinant receptor technique including the site-directed mutagenesis. Local anesthetics inhibited the NMDA receptor function in dose-dependent manners. The rank order in the potencies of local anesthetics to the NMDA receptor were different from that to voltage-sensitive Na channel. The site of action for procaine was related to that for ketamine and Mg+. Then we tried to examine the effect of general anesthetics such N2O and xenon which posses the analgesic actions on the 5-HT3 receptor. These gas anesthetics dose-dependently inhibited the 5-HT3 receptor. In contrast volatile anesthetics such as isoflurane and halothane except sevoflurane potentiated the 5-HT3 receptor function. In this investigation we addressed to the specific interactions of the neuropathic drugs and central nervous receptors related to the pain sensation such as NMDA and 5HT3 receptors.
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