| Co-Investigator(Kenkyū-buntansha) |
SEKIYAMA Hiroshi The University of Tokyo, Faculty of Medicine, Project Lecturer, 医学部附属病院, 特任講師 (40301105)
HANAOKA Kazuo The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (80010403)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
1. Previous studies with the rat chronic constriction injury (CCI) model have shown that Sokei-kakketsu-to suppressed increased hypersensitivity to mechanical or heat stimuli ; and its mechanism of action is via noradrenergic activation of the descending inhibitory system. On the other hand, in similar studies on Keishi-ka-jutsubu-to and Shinbu-to, no suppression of increased hypersensitivity was observed.
2. Processed Aconiti tuber, a Chinese herbal medicine, suppressed increased hypersensitivity to heat or pressure stimuli dose-dependently in a rat CCI model, and it was suggested that part of the mechanism of action was via kappa-opioid receptor. Lactoferrin, administered intrathecally or intraperitoneally, also suppressed hypersensitivity to heat or mechanical stimuli, dose-dependently, and it was suggested that the action was via mu-opioid receptor. Moreover, combined administration of processed Aconiti tuber and lactoferrin, both at sub-analgesic doses, showed a hypersensitivity su
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ppressing effect, suggesting lactoferrin may enhance the hypersensitivity suppressing effect of processed Aconiti tuber.
3. The suppressing effect of processed Aconiti tuber on morphine tolerance was investigated using mice. Sub-analgesic doses of processed Aconiti tuber dose-dependently suppressed the morphine tolerance induced by cyclic administration of morphine (once a day for seven days). It was indicated that this action was mainly due to mesaconitine, a constitutive alkaloid. Even after morphine tolerance had developed, processed Aconiti tuber was shown to reverse the tolerance. Those morphine tolerance suppressing actions of processed Aconiti tuber have been proved to be via kappa-opioid receptor. Then, morphine tolerance suppressing effects were investigated regarding U50488H, a selective kappa-opioid receptor agonist, and MK-801, an NMDA receptor antagonist. U50488H inhibited development of morphine tolerance, and it also had a tolerance-reversing action on established tolerance. On the other hand, although MK-801 suppressed the development of morphine tolerance, it failed to abolish morphine tolerance that had already been established. Less
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