2007 Fiscal Year Final Research Report Summary
A fundamental study for application of nitric oxide to a diagnosis and treatments of the chronic pain
| Project/Area Number |
18613023
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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 | Kansai Medical University |
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Principal Investigator |
ABE Tetsuya Kansai Medical University, Faculty of Medicine, Assistant Professor (20411506)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Shinji Kansai Medical University, Faculty of Medicine, Assistant Professor (70276393)
FUKUNAGA Mikihiko Kansai Medical University, Faculty of Medicine, Associate Professor (90257949)
NAKAI Yoshihide Kansai Medical Univerity, Faculty of Medicine, Professor (00091281)
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| Project Period (FY) |
2006 – 2007
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| Keywords | nitric oxide / neuropathic pain / primary afferent / NMDA receptor / spinal cord / enzymohistochemistry / Imaging / mice |
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| Research Abstract |
We established an ex vivo system to elucidate biochemical and molecular mechanisms for nNOS activation by the use of a combination of isolated intact spinal cord preparations and NADPH-diaphorase histochemistry.
Nociceptin/orphanin FQ (N/OFQ) was earlier shown to be involved in the maintenance of neuropathic pain by activating neuronal nitric oxide synthase (nNOS). We examined the N/OFQ signal pathways coupled to nNOS activation in the spinal cord by using this ex vivo system. N/OFQ enhanced nNOS activity in the superficial layer of the spinal cord, as assessed by NADPH-diaphorase histochemistry, in a time- and dose-dependent manner. The maximum effect was observed at 3-10 nM. The N/OFQ-stimulated nNOS activity was inhibited by NMDA receptor antagonists MK-801 and D-AP5, but not by the NR2B-selective antagonist; and the stimulated activity was observed in NR2D(-/-) mice, but not in NR2A(-/-) or NR2A(-/-)/NR2D(-/-) mice. N/OFQ receptor antagonists attenuated the nNOS activity stimulated
… More
by N/OFQ, but not that by NMDA. N/OFQ stimulated nNOS activity by a biochemical cascade initiated by activation of NMDA receptors containing NR2A.
To clarify whether NO itself affected nNOS activity in the spinal cord as a retrograde messenger, we examined the involvement of the NO/cGMP signaling pathway in the regulation of nNOS activity. NO-generating agents enhanced NADPH-diaphorase staining in the spinal cord 8-Br-cGMP also enhanced it similar to that by NO-generating agents, and 8-Br-cAMP and forskolin, an activator of adenylate cyclase, enhanced it moderately. NO-generating agents markedly increased the cGMP level in the spinal cord. Additionally, the nNOS activation was completely inhibited by NMDA antagonists MK-801 and d-AP5, partially by the NR2B-selective antagonist, and was attenuated in NR2A(-/-) and NR2A(-/-)/2D(-/-) mice. These results suggest that NO may regulate nNOS activity as a retrograde messenger in the spinal cord via activation of NMDA receptor containing NR2A and NR2B subunits. Less
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Research Products
(49 results)
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[Journal Article] Involvement of stem cell factor and its receptor tyrosine kinase c-kit in pain regulation2008
Author(s)
Takagi K, Okuda-Ashitaka E, Mabuchi T, Katano T, Ohnishi T, Matsumura S, Ohnaka M, Kaneko S, Abe T, Hirata T, Fujiwara S, Minami T and Ito S.
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Journal Title
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Involvement of stem cell factor and its receptor tyrosine kinase c-kit in pain regulation2008
Author(s)
Takagi K, Okuda-Ashitaka E, Mabuchi T, Katano T, Ohnishi I, Matsumura S. Ohnaka M, Kaneko S. Abe T, Hirata T, Fujiwara S, Minami T, Ito S.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cytotoxicity of spermine on retinal pigment epithelial cells2007
Author(s)
Kaneko, S., Ueda-Yamada, M., Ando, A., Matsumura, S., Okuda-Ashitaka, E., Matsumura, M., Uyama, M. and Ito, S.
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Journal Title
Investigative Ophthalmology and Visual Science 48
Pages: 455-463
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Signal pathways coupled to activation of neuronal nitric oxide synthase in the spinal cord by nociceptin/orphanin FQ2007
Author(s)
Xu, L., Okuda-Ashitaka, E., Matsumura, S., Mabuchi, T., Okamoto, S., Sakimura, K., Mishina, M., and Ito, S.
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Journal Title
Neuropharmacology 52
Pages: 1318-1325
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] The opioid peptide nociceptin/orphanin FQ mediates prostaglandin E_2-induced allodynia,tactile pain associated with nerve injury2006
Author(s)
Okuda-Ashitaka, E., Minami, T., Matsumura, S., Takeshima, H., Reinscheid RK, Civelli, O and Ito S.
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Journal Title
European Journal of Neuroscience 23
Pages: 995-1004
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] In situmeasurement of neuronal nitric oxide synthase activity in the spinal cord by NADPH-disphorase histochemistry.2006
Author(s)
Xu, L., Matsumura S., Mabuchi, T., Takagi, K., Abe, T., Ito, S.
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Journal Title
Journal of Neuroscience Methods 150
Pages: 174-184
Description
「研究成果報告書概要(欧文)」より
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