Activated mechanism in the neuroplasticity change of nitric oxide, which is a diagnosis and the candidate of the treatment index

• Project/Area Number: 20602012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 疼痛学
• Research Institution: Kansai Medical University
• Principal Investigator: ABE Tetsuya Kansai Medical University, 医学部, 講師 (20411506)
• Co-Investigator(Kenkyū-buntansha): MATSUMURA Shinji 関西医科大学, 医学部, 講師 (70276393) ; FUKUNAGA Mikihiko 関西医科大学, 医学部, 教授 (90257949)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 慢性疼痛 / 一酸化窒素 / 神経可塑生 / 脊髄 / 後根神経節 / グルタミン酸 / NMDA受容体 / マウス / 神経可塑性

Research Abstract

Neuropathic pain produced by damage to or dysfunction of the nervous system is a common and severely disabling state that affects million of people worldwide. Fyn kinase-mediated phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 in the dorsal horn may have dual roles in the retention of NMDA receptors in the postsynaptic density and in activation of nitric oxide synthase. Y1472F-KI mice witha knock-in mutation of the Tyr1472 site to phenylalanine did not exhibit neuropathic pain induced by L5 spinal nerve transection.

Research Products

• [Journal Article] Characterization of nestin expression in the spinal cord of GFP transgenic mice after peripheral nerve injury. (2010)
  • Author(s): Matsumura S, Takagi K, Okuda-Ashitaka E, Lu J, Naritsuka H, Yamaguchi M, Ito S
  • Journal Title: Neuroscience 170 Pages: 921-953
  • Peer Reviewed
• [Journal Article] Impairment of CaMKII activation and attenuation of neuropathic pain in mice lacking NR2B phosphorylated at Tyr1472. (2010)
  • Author(s): Matsumura S, Kunori S, Mabuchi T, Katano T, Nakazawa T, 阿部哲也, Watanabe M, Yamamoto T, Okuda-Ashitaka E, Ito S
  • Journal Title: Eur.J.Neurosci. 32 Pages: 798-810
  • Peer Reviewed
• [Journal Article] A novel role of prostaglandin E2 in neuropathic pain : blockade of microglial migration in the spinal cord. (2010)
  • Author(s): Kunori S, Matsumura S, Okuda-Ashitaka E, Katano T, Audoly LP, Urade Y, Ito S
  • Journal Title: Glia 59 Pages: 208-209
  • Peer Reviewed
• [Journal Article] Characterization of nestin expression in the spinal cord of GFP transgenic mice after peripheral nerve injury. (2010)
  • Author(s): Matsumura S, Takagi K, Okuda-Ashitaka E, Lu J, Naritsuka H, Yamaguchi M, Ito S.
  • Journal Title: Neuroscience Volume: 170 Pages: 942-953
  • Peer Reviewed
• [Journal Article] Impairment of CaMKII activation and attenuation of neuropathic pain in mice lacking NR2B phosphorylated at Tyr1472. (2010)
  • Author(s): Matsumura S, Kunori S, Mabuchi T, Katano T, Nakazawa T, Abe T, Watanabe M, Yamamoto T, Okuda-Ashitaka E, Ito S.
  • Journal Title: European Journal of Neuroscience Volume: 32 Pages: 798-810
  • Peer Reviewed
• [Journal Article] A novel role of prostaglandin E_2 in neuropathic pain : blockade of microglial migration in the spinal cord. (2010)
  • Author(s): Kunori S, Matsumura S, Okuda-Ashitaka E, Katano T, Audoly L P, Urade Y, Ito S.
  • Journal Title: Glia Volume: 59 Pages: 208-218
  • Peer Reviewed
• [Journal Article] Translocation of neuronal nitric oxide synthase to the plasma membrane by ATP is mediated by P2X and P2Y receptors. (2009)
  • Author(s): Ohnishi T, Matsumura S, Ito S
  • Journal Title: Molecular Pain 5
  • Peer Reviewed
• [Journal Article] Involvement of prostaglandin F 2 alpha receptor in ATP-induced mechanical allodynia. (2009)
  • Author(s): Kunori S, Matsumura S, Mabuchi T, Tatsumi S, Sugimoto Y, Minami T, Ito S
  • Journal Title: Neuroscience 163 Pages: 362-371
  • Peer Reviewed
• [Journal Article] Translocation of neuronal nitric oxide synthase to the plasma membrane by ATP is mediated by P2X and P2Y receptors (2009)
  • Author(s): Ohnishi T, Matsumura S, Ito S
  • Journal Title: Molecular Pain 5
  • Peer Reviewed
• [Journal Article] Involvement of prostaglandin F2 alpha receptor in ATP-induced mechanical allodynia (2009)
  • Author(s): Kunori S, Matsumura S, Mabuchi T, Tatsumi S, Sugimoto Y, Minami T, Ito S
  • Journal Title: Neuroscience 163 Pages: 362-371
  • Peer Reviewed
• [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, 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, Ito S
  • Journal Title: J.Neurochem. 105 Pages: 2271-2285
  • 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] 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: Bio Clinic 23 Pages: 19-25
• [Journal Article] 日常診療におけるうつ病3) 痛みとの関連 (2008)
  • Author(s): 阿部哲也
  • Journal Title: 治療学 42 Pages: 151-154
• [Presentation] Attenuation of neuropathic pain by impaired Ca2+ signaling in mutant mice lacking the Tyr-1472 phosphorylation site of the NR2B (2010)
  • Author(s): Matsumura S, Kunori S, Nakazawa T, Abe T, Yamamoto T, Katano T, Watanabe M, Okuda-Ashitaka E, Ito S
  • Organizer: Sciety for Neuroscience
  • Place of Presentation: Sandiego, 米国
  • Year and Date: 2010-11-15
• [Presentation] Attenuation of neuropathic pain by impaired Ca^<2+> signaling in mutantmice lacking the Tyr-1472 phosphorylation site of the NR2B (2010)
  • Author(s): Matsumura S, Kunori S, Nakazawa T, Abe T, Yamamoto T, Katano T, Watanabe M, Okuda-Ashitaka E, Ito S
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego,米国
  • Year and Date: 2010-11-15
• [Book] 疼痛の理学療法 (2008)
  • Author(s): 阿部哲也
  • Publisher: 三輪書店
• [Remarks] ホームページ等
  • URL: http://image.tnoc.kmu.ac.jp/bmrc/
• [Patent(Industrial Property Rights)] 埋植用鎮痛製剤 (2010)
  • Inventor(s): 荒木吉朗、海堀昌樹、松村伸治、伊藤誠二、權雅憲
  • Industrial Property Rights Holder: 学校法人関西医科大学
  • Industrial Property Number: 2010-127252
  • Filing Date: 2010-06-02