| Project/Area Number |
10671450
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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 | Kansai Medical University |
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Principal Investigator |
IMANISHI Toshihiro Kansai Medical University, Anesthesiology, Assistant, 医学部, 助手 (70098119)
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| Co-Investigator(Kenkyū-buntansha) |
ASHITAKA Emiko (OKUDA Emiko) Kansai Medical University, Medical Chemistry, Lecturer, 医学部, 講師 (50291802)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | opioid / nocistatin / nociceptin / orphanin FQ(Noc / OFQ) / allodynia / hyperalgesia / capsaicin / glutamate / intrathecal administration / シセプチン / ホルマリンテスト / オピオイド受容体 / 痛覚反応 / 神経ペプチド / 前駆体蛋白 |
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| Research Abstract |
Opioid peptides are a family of neuropeptides with modulatory functions of nociception and inflammation. The heptadecapeptide called nociceptin or orprhanin FQ (Noc/OFQ) has recently been identifies as an endogenous ligand of the opioid receptor homologue, designated as ROR-C. Different from other known endogenous opioids which produce analgesic effects, we demonstrated that intrathecal (i.t.) administration of Noc/OFQ induces hyperalgesia to noxious stimuli and allodynia to innocuous tactile stimuli. We also demonstrated that allodynia induced by Noc/OFQ may be result from disinhibition of suppressive transmission by glycine. In the present study, we tried to elucidate the mechanism of pain responses induced by Noc/OFQ and newly obtained following results. 1) The Noc/OFQ-induced hyperalgesia is mediated by substance P and the Noc/OFQ-induced allodynia is mediated by glutamate through the NMDA receptor comprising the GluRε1 subunit, suggesting that different mechanisms are involved in
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these pain responses. 2) We used neonatal capsaicin treatment as a tool to destroy a population of primary afferents, most of which convey nociceptive inputs from the periphery to the spinal cord. This treatment eliminated the induction of hyperalgesia and allodynia by Noc/OFQ. Although allodynia was believed to be mediated by myelinated Aβfibers, we first demonstrated that capsaicin-sensitive primary afferent C fibers are involved not only in thermal hyperalgesia but also in tactile allodynia induced by Noc/OFQ. 3) Because the novel heptadecapeptide derived from the same precursor as Noc/OfQ has biological activity which blocks the Noc/OFQ-evoked pain transmission, we named it nocistatin. Nocistatin exhibits anti-nociceptive effects through a novel receptor different from known opioid receptors. This is the first report showing the existence of peptides with opposite effects on the same precursor protein. We plan to extend the present study on the mechanisms of pain transmission in the future. Less
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