A role of the nitric oxide in the plasticity expression mechanism of the spinal neural circuit which maintains a neuropathic pain

• Project/Area Number: 19603018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pain science
• Research Institution: Kansai Medical University
• Principal Investigator: MATSUMURA Shinji Kansai Medical University, 医学部, 講師 (70276393)
• Co-Investigator(Kenkyū-buntansha): ITO Seiji 関西医科大学, 医学部, 教授 (80201325)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 神経因性疼痛 / 脊髄 / 神経可塑性 / 一酸化窒素 / グルタミン酸 / NMDA受容体 / イメージング / マウス

Research Abstract

神経因性疼痛時脊髄後角神経回路において、脊髄後角のシナプス終末に存在するプロスタグランジンE2の受容体の一つであるEP1受容体活性化に伴うグルタミン酸遊離によりNMDA受容体がFynを介したチロシンのリン酸化により活性化され、神経型一酸化窒素(NO)合成酵素の細胞膜へ移動を伴う酵素活性の増大によりNO産生が上昇し、その産生の維持にはPKAとPKCの活性化が協同して行われていることが示唆された。

Research Products

• [Journal Article] Involvement of stem cell factor and its receptor tyrosine kinase c-kit in pain regulation (2008)
  • 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.
  • Journal Title: Neuroscience 153 Pages: 1278-1288
  • Peer Reviewed
• [Journal Article] Characterization of signaling pathway for the translocation of neuronal nitric oxide synthase to the plasma membrane by PACAP (2008)
  • Author(s): Ohnishi, T., Okuda-Ashitaka, E., Matsumura, S., Katano, T., Nishizawa, M. and Ito, S.
  • Journal Title: J. Neurochem 105 Pages: 2271-2285
  • Peer Reviewed
• [Journal Article] Natural Antisense Transcript Stabilizes Inducible Nitric Oxide Synthase mRNA in Rat Hepatocytes (2008)
  • Author(s): Matsui, K., Nishizawa, M., Ozaki, T., Kimura, T., Hashimoto, I., Yamada, M., Kaibori, M., Kamiyama, Y., Ito, S. and Okumura,T.
  • Journal Title: Hepatol 47 Pages: 686-697
  • Peer Reviewed
• [Journal Article] Studies on membrane-associated prostaglandin E synthase-2 with reference to production of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) (2008)
  • Author(s): Watanabe, K., Ito, S. and Yamamoto, S.
  • Journal Title: Biochem Biophys Res Commun. 367 Pages: 782-786
  • Peer Reviewed
• [Journal Article] Molecular Characterization of a Novel Type of Prostamide/Prostaglandin F Synthase, Belonging to the Thioredoxin-like Superfamily (2008)
  • Author(s): Moriuchi, H., Koda, N., Okuda-Ashitaka, E., Daiyasu, H., Ogasawara, K., Toh, H., Ito, S., David F. Woodward and Watanabe, K.
  • Journal Title: J. Biol. Chem. 283 Pages: 792-801
  • Peer Reviewed
• [Journal Article] Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in proinflammatory cytokine-stimulated hepatocytes (2008)
  • Author(s): Habara, K., Hamada, Y., Yamada, M., Tokuhara, K., Tanaka, H., Kaibori, M., Kamiyama, Y., Nishizawa, M., Ito, S. and Okumura, T.
  • Journal Title: Nitric Oxide 18 Pages: 19-27
  • Peer Reviewed
• [Journal Article] Rebamipide, anti-gastric ulcer drug, up-regulates the induction of iNOS in proinflammatory cytokine-stimulated hepatocytes (2008)
  • Author(s): Tokuhara, K., Hamada, Y., Tanaka, H., Yamada, M., Ozaki, T., Matsui, K., Kamiyama, Y., Nishizawa, M., Ito, S. and Okumura, T.
  • Journal Title: Nitric Oxide 18 Pages: 28-36
  • Peer Reviewed
• [Journal Article] Na+/H+ exchanger inhibitor, FR183998, has protective effect in lethal acute liver failure and prevents iNOS induction in rats (2008)
  • Author(s): Tanaka, T., Uchida, Y., Kaibori, M., Hijikawa, T., Ishizaki, M., Yamada, M., Matsui, K., Ozaki, T., Tokuhara, K., Kamiyama, Y., Nishizawa, M., Ito, S. and Okumura, T.
  • Journal Title: J Hepatol 48 Pages: 289-299
  • Peer Reviewed
• [Journal Article] Edaravone prevents iNOS expression by inhibiting its promoter transactivation and mRNA stability in cytokine-stimulated hepatocytes (2008)
  • Author(s): Yoshida, H., Know, A., Kaibori, M., Tsuji, K., Habara, K., Yamada, M., Kamiyama, Y., Nishizawa, Ito, S. and Okumura,T.
  • Journal Title: Nitric Oxide 18 Pages: 105-112
  • Peer Reviewed
• [Journal Article] N-Ethylmaleimide-sensitive fusion protein(NSF) is involved in central sensitization in the spinal cord through GluR2 subunit composition switch after inflammation (2008)
  • Author(s): Katano, T., Furue, H., Okuda-Ashitaka, E., Tagaya, M., Watanabe, M., Yoshimura, M. and Ito, S.
  • Journal Title: Eur. J. Neurosci. 27 Pages: 3161-3170
  • Peer Reviewed
• [Journal Article] 痛みにおけるNOの関与 (2008)
  • Author(s): 松村伸治、阿部哲也、芦高恵美子、伊藤 誠二
  • Journal Title: Bio Clinica 第23巻第5号 Pages: 19-25
• [Journal Article] アクロメリン酸と痛み (2008)
  • Author(s): 荘園雅子、南敏明、伊藤誠二
  • Journal Title: ペインクリニック 第29巻第3号 Pages: 351-364
• [Journal Article] Characterization of signaling pathway for the translocation of neuronal nitric oxide synthase to the plasma membrane by PACAP. (2008)
  • Author(s): Ohnishi T
  • Journal Title: J. Neurochem. 105 Pages: 2271-2285
  • Peer Reviewed
• [Journal Article] Involvement of stem cell factor and its receptor tyrosine kinase c-kit in pain regulation. (2008)
  • Author(s): Takagi, K
  • Journal Title: Neuroscience 153 Pages: 1278-1288
  • Peer Reviewed
• [Journal Article] 痛みにおけるNOの関与 (2008)
  • Author(s): 松村伸治
  • Journal Title: BioClinica 23 Pages: 397-403
• [Journal Article] 痛みにおけるNOの関与 (2008)
  • Author(s): 松村 伸治
  • Journal Title: バイオクリニカ 23 Pages: 397-403
• [Journal Article] Signal pathways coupled to activation of neuronal nitric oxide synthase in the spinal cord by nociceptin/orphanin FQ (2007)
  • Author(s): Xu, L., Okuda-Ashitaka, E., Matsumura, S., Mabuchi, T., Okamoto, S., Sakimura, K., Mishina ,M. and Ito, S.
  • Journal Title: Neuropharmacology 52 Pages: 1318-1325
  • Peer Reviewed
• [Journal Article] Cytotoxic effect of spermine on retinal pigment epithelial cells (2007)
  • Author(s): Kaneko, S., Ueda-Yamada, M., Ando, A., Matsumura, S., Okuda-Ashitaka, E., Matsumura, M., Uyama, M. and Ito, S.
  • Journal Title: Invest. Ophthalmol. Vis. Sci. 48 Pages: 455-463
  • Peer Reviewed
• [Journal Article] Interleukin-1 is not essential for expression of inducible NOS in hepatocytes induced by lipopolysaccharide in vivo (2007)
  • Author(s): Takagi, K., Matsumura, S., Okuda-Ashitaka, E., Okuda, K., Watanabe, J., Takahashi,H., Iwakura, Y. and Ito, S.
  • Journal Title: Nitric Oxide 16 Pages: 433-441
  • Peer Reviewed
• [Journal Article] Nitric oxide (NO) serves as a retrograde messenger to activate neuronal NO synthase in the spinal cord via NMDA receptors (2007)
  • Author(s): Xu, L., Mabuchi, T., Katano, T., Matsumura, S., Okuda-Ashitaka, E., Sakimura, K., Mishina ,M. and Ito, S.
  • Journal Title: Nitric oxide 17 Pages: 18-24
  • Peer Reviewed
• [Journal Article] Ornithine transport via cationic amino acid tansporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells (2007)
  • Author(s): Kaneko, S., Ando, A., Okuda-Ashitaka, E., Maeda, M., Fruta, K., Suzuki, M., Matsumura, M. and Ito, S.
  • Journal Title: Invest. Ophthalmol. Vis. Sci. 48 Pages: 464-471
  • Peer Reviewed
• [Journal Article] Senescence in cultured trabecular meshwork cells (2007)
  • Author(s): Yamazaki, Y., Matsunaga, H., Nishikawa, M., Ando, A., Kaneko, S., Okuda, K., Wada,M., Ito, S. and Matsumura,M.
  • Journal Title: Br. J. Ophthalmol. 91 Pages: 808-811
  • Peer Reviewed
• [Journal Article] Ovol2/Movo, a homologue of Drosophila ovo, is required for angiogenesis, heart formation and placental development in mise (2007)
  • Author(s): Unezaki, S., Horai, R., Sudo, K., Iwakura, Y. and Ito, S.
  • Journal Title: Genes Cells 12 Pages: 773-785
  • Peer Reviewed
• [Journal Article] Effect of thiol-containing molecule cysteamine on the induction of inducible nitric oxide synthase in hepatocytes (2007)
  • Author(s): Ozaki, T., Kaibori, M., Matsui, K., Tokuhara, K., Tanaka, H., Kamiyama, Y., Nishizawa, M., Ito, S. and Okumura, T.
  • Journal Title: JPEN. J. Parenteral Enteral Nutr. 31(5) Pages: 366-372
  • Peer Reviewed
• [Journal Article] Polyamines up-regulate the mRNA .expression of cationic amino acid transporter-1 in human retinal pigment epithelial cells (2007)
  • Author(s): Kaneko, S., Okuda-Ashitaka, E., Ando, A., Nishimura, K., Igarashi, K., Maeda, M., Furuta, K., Suzuki, M., Matsumura, M. and Ito, S.
  • Journal Title: Am.J. Physiol. 293
  • Peer Reviewed
• [Journal Article] Characterization of alternatively spliced isoforms of the type I interleukin-1 receptor on iNOS induction in rat hepatocytes (2007)
  • Author(s): Yamada, M., Nishizawa, M., Nakatake, R., Habara, K., Yoshida, H., Ozaki, T., Matsui, K., Hamada, Y., Kamiyama, Y., Ito, S. and Okumura,T.
  • Journal Title: Nitric Oxide-Biol Chem 17 Pages: 98-105
  • Peer Reviewed
• [Journal Article] A synthetic kainoid, (2S,3R,4R)-3-carboxymethyl-4-(phenylthio) pyrrolidine-2-carboxylic acid (PSPA-1) serves as a novel analgesic for neuropathic pain (2007)
  • Author(s): Soen, M., Minami, T., Tatsumi, S., Mabuchi, T., Fruta, K., Maeda, M., Suzuki, M. and Ito, S.
  • Journal Title: Eur. J. Pharmacol. 575 Pages: 75-81
  • Peer Reviewed
• [Journal Article] Different roles of nitric oxide synthase-1 and -2 between herpetic and postherpetic allodynia in mice (2007)
  • Author(s): Sasaki, A., Mabuchi, T., Serizawa, K., Takasaki, I., Andoh, T., Shiraki, K., Ito, S. & Kuraishi, Y.
  • Journal Title: Neuroscience 150 Pages: 459-466
  • Peer Reviewed
• [Journal Article] 脊髄後角におけるNMDA受容体リン酸化と神経因性疼痛 (2007)
  • Author(s): 芦高恵美子、阿部哲也、松村伸治、伊藤誠二
  • Journal Title: 慢性疼痛 第26巻第1号 Pages: 41-47
• [Journal Article] シナプス後肥厚部のNMDA受容体のリン酸化と神経因性疼痛 (2007)
  • Author(s): 片野泰代、伊藤誠二
  • Journal Title: 生体の科学 第58巻第2号 Pages: 39-143
• [Journal Article] 慢性疼痛研究の最近の進歩~機能的変化による慢性疼痛の維持機構~ (2007)
  • Author(s): 伊藤誠二
  • Journal Title: ペインクリニック 第28巻第2号 Pages: 199-207
• [Journal Article] 慢性疼痛の発生維持機構について (2007)
  • Author(s): 伊藤誠二
  • Journal Title: ペインクリニック 第28巻別冊春号 Pages: 326-328
• [Journal Article] 痛覚の発生機序の最前線 (2007)
  • Author(s): 伊藤誠二
  • Journal Title: Urology View 第5巻第5号 Pages: 8-14
• [Journal Article] プロスタグランジンとノシセプチン (2007)
  • Author(s): 南敏明、芦高恵美子、伊藤誠二
  • Journal Title: 麻酔 第56巻増刊号
• [Journal Article] Cytotoxic effect of spermine on retinal pigment epithelial cells (2007)
  • Author(s): Kaneko S
  • Journal Title: Invest Ophthalmol Vis Sci 48 Pages: 455-463
  • Peer Reviewed
• [Journal Article] Signal pathways coupled to activation of neuronal nitric oxide synthase in the spinal cord by nociceptin/0rphanin FQ (2007)
  • Author(s): Xu L
  • Journal Title: Neuropharmacology 52 Pages: 1318-1325
  • Peer Reviewed
• [Journal Article] Interleukin-1 is not essential for expression of inducible NOS in hepatocytes induced by lipopolysaccharide in vivo (2007)
  • Author(s): Takagi K
  • Journal Title: Nitric Oxide 16 Pages: 433-441
  • Peer Reviewed
• [Journal Article] Nitric oxide(NO)serves as a retrograde messenger to activate neuronal NO synthase in the spinal cord via NMDA receptors (2007)
  • Author(s): Xu L
  • Journal Title: Nitric Oxide 17 Pages: 18-24
  • Peer Reviewed
• [Presentation] Effect of neurotrophic factors on nerve regeneration monitored by in vivo imaging in the thy1-YFP transgenic mice (2008)
  • Author(s): Ito, S., Unezaki, S., Mabuchi, T., Saito, A. and Yoshii, S.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2008-11-16
• [Presentation] Effect of neurotrophic factors on nerve regeneration monitored by in vivo imaging in the thyl-YFP transgenic mice (2008)
  • Author(s): Ito S
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2008-11-16
• [Presentation] Differentiation and migration of progenitor cells for maitenance of neuropathic pain in the model using nestin promoter-GFP transgenic mice (2007)
  • Author(s): Matsumura, S. Takagi, K., Okuda-Ashitaka, E., Yamaguchi, M. and Ito, S.
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2007-11-04
• [Presentation] Nitric oxide is involved in activation of neuronal nitric oxide synthase as a retrograde messenger in the spinal cord (2007)
  • Author(s): Ito, S., Xu, L., Mabuchi, T., Katano, T., Matsumura, S., Okuda-Ashitaka, E., Sakimura, K. and Mishina, M.
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2007-11-04
• [Presentation] Signal pathways coupled to activation of neuronal nitric oxide synthase in the spinal cord by nociceptin/orphanin FQ (2007)
  • Author(s): Okuda-Ashitaka, E. Xu, L., Matsumura, S., Mabuchi, T., Sakimura, K., Mishina, M. and Ito, S.
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2007-11-04
• [Presentation] Molecular mechanism for the translocation of nNOS to the plasma membrane by PACAP (2007)
  • Author(s): Ohnishi, T., Okuda-Ashitaka, E., Matsumura, S. and Ito, S.
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 2007-11-04
• [Presentation] Signal pathways coupled to activation of neuronal nitric oxide synthase in the spinal cord by nociceptin/orphanin FQ (2007)
  • Author(s): Okuda-Ashitaka E
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego,USA
  • Year and Date: 2007-11-04
• [Presentation] Differentiation and migration of progenitor cells for maitenance of neuropathic pain in the model using nestin promoter-GFP transgenic mice (2007)
  • Author(s): Matsumura S
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego,USA
  • Year and Date: 2007-11-04
• [Presentation] Nitric oxide is involved in activation of neuronal nitric oxide synthase as a retrograde messenger in the spinal cord (2007)
  • Author(s): Ito S
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego,USA
  • Year and Date: 2007-11-04
• [Presentation] Molecular mechanism for the translocation of nNOS to the plasma membrane by PACAP (2007)
  • Author(s): Ohnishi T
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego,USA
  • Year and Date: 2007-11-04