2009 Fiscal Year Final Research Report
The roles of neuronal calcium channels on the physiological functions of opioid analgesics
Project/Area Number |
19603002
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pain science
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
KURIHARA Takashi Tokyo Medical and Dental University, 医歯学総合研究科, 助教 (60282745)
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Project Period (FY) |
2007 – 2009
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Keywords | オピオイド / モルヒネ / 電位依存性カルシウムチャネル / 鎮痛 / 鎮痛耐性 / cDNAマイクロアレイ |
Research Abstract |
Opioids like morphine exert strong analgesic effects and have essential therapeutic values to eliminate intractable pain. Thus opioid drugs became indispensable medicine to improve the quality of life of pain patient. However, opioid tolerance and dependence are difficult problems associated with the opioid therapy and opioid addiction. Unfortunately, efficient method to prevent analgesic tolerance based on the underlying mechanism has not been developed yet. We have shown previously that mice lacking R-type voltage-dependent Ca^<2+> channel showed enhanced morphine analgesia but also showed resistance to morphine tolerance. To identify molecules responsible for the altered analgesic responses, we have conducted cDNA microarray analysis using brainstem tissues and found several candidate genes involved in the altered morphine responses. The results from several pharmacological, biochemical and immunohistochemical experiments suggested the existence of new signal transduction mechanisms in the development of morphine tolerance in the brainstem area. We have also indicated that it might be possible to induce tolerance against morphine-evoked constipation by manipulating pharmacologically the similar signal transduction existed in the intestine.
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[Journal Article] Peripheral-type benzodiazepine receptor antagonist is effective in relieving neuropathic pain in mice2009
Author(s)
Kondo, D., Saegusa, H., Yabe, R., Takasaki, I., Kurihara, T., Zong, S., Tanabe, T.
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Journal Title
J.Pharmacol.Sci. 110
Pages: 55-63
Peer Reviewed
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[Journal Article] Upregulation of casein kinase 1ε in dorsal root ganglia and spinal cord after mouse spinal nerve injury contributes to neuropathic pain2009
Author(s)
Sakurai, E., Kurihara, T., Kouchi, K., Saegusa, H., Zong, S, Tanabe, T.
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Journal Title
Peer Reviewed
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