2000 Fiscal Year Final Research Report Summary
Studies on Mechanism of Intractable Pain wih Animal Models
| Project/Area Number |
11470329
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 Medical College |
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Principal Investigator |
MINAMI Toshiaki Faculty of Medicine, Osaka Medical College Research Associate, 医学部, 助手 (00257841)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Kohji 塩野義製薬(株), 新薬研究所・薬理評価部門, 研究員
ENOMOTO Utako 大阪医科大学, 医学部, 助手 (00278516)
HARA Naoki Osaka Medical College, 医学部, 助手 (60298768)
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| Project Period (FY) |
1999 – 2000
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| Keywords | allodynia / pain / nocistatin / nociceptin / glutamate receptor / prostaglandins / knockout mice |
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| Research Abstract |
Mechanism of PG-induced allodynia
We previously showed that intrathecal (i.t.) administration of PGE 2 and PGF2αinduce touch-evoked pain (allodynia) in conscious mice. Selective elimination of C-fibers by neonatal capsaicin treatment results in the disappearance of allodynia induced by PGE 2, but not byPGF2α. PGE2- induced allodynia was not observed in NMDA receptor ε1 subunit knockout mice and sensitive to morphine. In contrast, PGF2α-induced one was not observed in NMDA ε4 subunit knockout mice and insensitive to morphine. The induction of allodynia by PGE 2 was abolished by the NMDA, receptor ε2 antagonist CP-101, 606. PGF2 α-induced allodynia was not affected by CP- 101, 606. These results demonstrate that there are two pathways for induction of allodynia mediated by the glutamatergic system.
Roles of nociceptin and nocistatin in pain transmission
We recently showed that i.t. administration of nociceptin induced thermal hyperalgesia and tactile allodynia. In the present study, we demonstrate that capsaicin-sensitive primary afferent fibers are involved not only in thermal hyperalgesia but also in tactile allodynia induced by nociceptin, but in different pathways ; the former is mediated by substance P and the latter is mediated by glutamate through the NMDA receptor comprising GluR ε1 subunit. On the other hand, nocistatin is derived from the same precursor as nociceptin, and it has biological activity which blocks the nociceptin- and PGs-evoked pain responses. Furthermore nocistatin blocks both the early and the late phases in the formalin test.
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Research Products
(22 results)
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[Publications] Minami, T., Okuda-Ashitaka, E., Mori, H., Sakuma, S., Sugimoto T., Sakimura, K., Mishina, M., and Ito, S.: "Involvement of primary afferent C-fibers in touch-evoked pain (allodynia) induced by prostaglandin E2."Eur.J Neurosci.. 11. 1849-1856 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakano, H., Minami, T., Abe, K., Arai, T., Tokumura, M., Ibii, N., Okuda-Ashitaka, E., Mori, H., and Ito, S.: "Effect of intrathecal nocistatin on the formalin-induced pain in mice versus that of nociceptin/orphanin FQ."J.Pharmacol.Exp.Ther.. 292. 331-336 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Minami, T., Okuda-Ashitaka, E., Mori, H., Sakimura, K., Watanabe, M., Mishina, M., and Ito, S.: "Characterization of nociceptin/orphanin FQ-induced pain responses in conscious mice : neonatal capsaicin treatment and NMDA receptor GluR ε subunit konokout mice."Neuroscience. 97. 133-142 (3000)
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「研究成果報告書概要(欧文)」より
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[Publications] Minami, T., Matsumura, S., Okuda-Ashitaka, E., Shimamoto, K., Sakimura, K., Mishina, M., Mori, H., and Ito, S.: "Characterization of the glutamatergic system for induction and maintenance of allodynia."Brain Res.. (in press.).
Description
「研究成果報告書概要(欧文)」より
