Drug discovery and the mechanism of neuropathic pain targeting central cholinergic systems
| Project/Area Number |
19603022
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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 |
Pain science
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| Research Institution | Fukuoka University |
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Principal Investigator |
HONDA Kenji Fukuoka University, 薬学部, 助教 (60140761)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Ryo 福岡大学, 薬学部, 講師 (80122696)
TAKANO Yukio 福岡大学, 薬学部, 教授 (50113246)
MIGITA Keisuke 弘前大学, 大学院・医学研究科, 助教 (10352262)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 神経障害性疼痛 / 中枢性ムスカリン受容体 / GABA作動性神経 / ミクログリア細胞 / ケモカイン / 帯状回皮質 / ムスカリンM1受容体 / グリア細胞 / ミノサイクリン / 脊髄ケモカイン / CCL / 神経因性疼痛 / アロディニア / 前頭部帯状回皮質 / ムスカリン受容体 / ミクログリア / コリン作動性神経 / 坐骨神経部分損傷 / 脊髄 / 脳内ムスカリン受容体 / GABA受容体 / アストロサイト |
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| Research Abstract |
(1) In this study, we examined the mechanism of neuropathic pain in spinal cord and brain. Especially, we demonstrated how the muscarinic receptors in spinal cord and brain involve in neuropathic pain. Activation of spinal muscarinic M_1, receptors produces analgesic effect to nociceptive stimulation and, at least in part, through neuronal pathways involving spinal GABA_A receptors. In addition, Activation of muscarinic M_1 receptors in the the cinglate cortex attenuated the neuropathic pain and the analgesic effect was mediated by both GABA_A and GABA_B receptors. (2) In addition, we examined the functional role of chemokines in neuropathic pain. Pre-administrations of microglia inhibitor minocycline inhibited the allodynia. This result supports that Chemotactic Cytokine Ligand (CCL)-1 in the spinal cord contributes to the development of neuropathic pain.
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] Aldosterone-sensitive NTS neurons regulate sensitivity of the baroreceptor reflex in high-sodium loaded rats2010
Author(s)
Masuda T, Hirabara Y, Nakamura Y, Chishaki A, Tsuruhisa M, Miyakawa M, Honda K, Saito R, Sakamoto H, Kawata M, TakanoY
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Journal Title
J. Pharmacol. Sci. Vol.112
Pages: 482-486
Related Report
Peer Reviewed
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[Journal Article] Aldosterone-sensitive NTS neurons regulate sensitivity of the baroreceptor reflex in high-sodium loaded rats2010
Author(s)
Masuda T, Hirabara Y, Nakamura Y, Chishaki A, Tsuruhisa M, Miyakawa M, Honda K, Saito R, Sakamoto H, Kawata M, Takano Y
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Journal Title
J.Pharmacol.Sci. 112(In press)
Related Report
Peer Reviewed
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[Journal Article] Involvement of Na+/Ca2+ exchanger in pentylenetetrazol-induced convulsion by use of Na+/Ca2+ exchanger knockout mice2009
Author(s)
Saito R., Kaneko, E., Tanaka, Y., Honda, K., Matsuda, T., Baba, A., Komuro, I., Kita, S., Iwamoto, T., Takano Y.
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Journal Title
Biol.Pharma.Bull. 32
Pages: 1298-1930
NAID
Related Report
Peer Reviewed
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[Journal Article] Contribution of Ca^<2+>-dependent protein kinase C in the spinal cord to the development of mechallical allodynia in diabetic mice2007
Author(s)
Honda, K. Koguchi, M., Koga, K., Nakajima, K., Kobayashi, F., Migita, K., Ogata, S., Hirabara, Y., Takano, Y
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Journal Title
Biological and Pharmaceutical Bulletin 30
Pages: 990-993
Related Report
Peer Reviewed
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[Journal Article] A high-sodium diet in streptozotocin-induced diabetic rats impairsendothelium-derived hyperpolarizing factor-mediated vasodilation2007
Author(s)
Hirabara, Y, Araki, M., FukUda, M., Katafuchi, S., Honda, K., Saito, R., and Takano, Y.
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Journal Title
J.Pharmacol.Sci 104
Pages: 402-405
Related Report
Peer Reviewed
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[Presentation] 糖尿病・食塩負荷モデルラットにおいて動脈圧受容器反射は減弱する;弧束核におけるアルドステロン感受性神経2009
Author(s)
増田大治, 中村祐介, 宮川雅行, 平原康寿, 本多健治, 斎藤亮, 有森和彦, 中川裕之, 坂本浩隆, 河田光博, 高野行夫
Organizer
第82回日本薬理学会年会
Place of Presentation
横浜
Year and Date
2009-03-16
Related Report
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