The role of purinergic receptor in the spinal microglia following peripheral nerve injury

• Project/Area Number: 19790159
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: Hyogo College of Medicine
• Principal Investigator: KOBAYASHI Kimiko Hyogo College of Medicine, 医学部, 助教 (70418961)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,620,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: プリン受容体 / 神経因性痙痛 / 脊髄後角 / マイクログリア / P2Y受容体 / アストロサイト / MAPキナーゼ / 神経因性疼痛 / ATP / UTP / P2Y receptor / microglia / MAP kinase / p38

Research Abstract

活性化マイクログリアの増加が神経因性痺痛に関与し、またマイクログリアの活性化にはATPが関与することが示唆されていたが詳細なメカニズムが不明であった為、ATP受容体に着目して研究を行った。2007年度はマイクログリアに定常的に発現する代謝型P2Y12受容体が神経因性疼痛発生の初期段階で関与することをつきとめ、2008年度は末梢神経損傷後の脊髄後角マイクログリアにおいてP2Y6,13,14受容体が増加することが分かった。

Research Products

• [Journal Article] P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain (2008)
  • Author(s): Kobayashi K, Yamanaka H, Fukuoka T, Dai Y, Obata K, Noguchi K
  • Journal Title: J. Neurosci 28 Pages: 2892-902
• [Journal Article] Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons (2008)
  • Author(s): Fukuoka T, Kobayashi K, Yamanaka H, Obata K, Dai Y and Noguchi K
  • Journal Title: J. Comp. Neurol 10, 510 Pages: 188-206
• [Journal Article] Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalgesia (2008)
  • Author(s): Cui XY, Dai Y, Wang SL, Yamanaka H, Kobayashi K, Obata K, Chen J, Noguchi K.
  • Journal Title: Mol Pain 30,4(1) Pages: 17-17
• [Journal Article] Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1 : a molecular mechanism of inflammatory pain (2008)
  • Author(s): Wang S, Dai Y, Fukuoka T, Yamanaka H, Kobayashi K, Obata K, Cui X, Tominaga M, Noguchi K.
  • Journal Title: Brain 131 Pages: 1241-1251
• [Journal Article] P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain (2008)
  • Author(s): Kobayashi, K., et.al.
  • Journal Title: J. Neurosci 28 Pages: 2892-2902
  • Peer Reviewed
• [Journal Article] Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons (2008)
  • Author(s): Fukuoka, T., et.al.
  • Journal Title: J. Comp. Neurol 510 Pages: 188-206
  • Peer Reviewed
• [Journal Article] Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1 : a molecular mechanism of inflammatory pain (2008)
  • Author(s): Wang, S., et.al.
  • Journal Title: Glia 56 Pages: 723-733
  • Peer Reviewed
• [Journal Article] Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalcresia (2008)
  • Author(s): Cui, X. Y., et.al.
  • Journal Title: Mol. Pain
  • Peer Reviewed
• [Journal Article] Transforming growth factor-activated kinase 1 induced in spinal astrocytes contributes to mechanical hypersensitivity after nerve injury (2008)
  • Author(s): Katsura, H., et. al.
  • Journal Title: Glia (in press)
  • Peer Reviewed
• [Journal Article] P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain (2008)
  • Author(s): Kobayashi, K., et. al.
  • Journal Title: J. Neurosci. 28 Pages: 2892-2902
  • Peer Reviewed
• [Journal Article] Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain (2008)
  • Author(s): Wang, S., et. al.
  • Journal Title: Brain (in press)
  • Peer Reviewed
• [Journal Article] Alternation of the cell adhesion molecule Ll expression in a specific subset of primary afferent neurons contributes to neuropathic pain (2007)
  • Author(s): Yamanaka, H., Obata, K, Kobayashi, K., Dai, Y., Fukuoka, T., Noguchi, K.
  • Journal Title: Eur. J. Neurosci 25 Pages: 1097-111
• [Journal Article] Tissue type plasminogen activator induced in rat dorsal horn astrocytes contributes to mechanical hypersensitivity following dorsal root injury (2007)
  • Author(s): Kozai, T., Yamanaka, H., Dai, Y., Obata, K., Kobayashi, K., Mashimo, T. and Noguchi, K
  • Journal Title: Glia 55 Pages: 595-603
• [Journal Article] Sensitization of TRPA1 by PAR-2 through PLC/PIP2-dependent mechanisms contributes to inflammatory pain (2007)
  • Author(s): Dai, Y., Wang, S., Tominaga, M., Yamamoto, S., Fukuoka, T., Higashi, T., Kobayashi, K., Obata, K., Yamanaka, H., Noguchi, K.
  • Journal Title: J. Clin. Invest 117 Pages: 1979-1987
• [Journal Article] Activation of fibroblast growth factor receptor by axotomy, through downstream p38 in dorsal root ganglion, contributes to the neuropathic pain (2007)
  • Author(s): Yamanaka, H., Obata, K., Kobayashi, K., Dai, Y., Fukuoka, T., Noguchi, K.
  • Journal Title: Neuroscience 150 Pages: 202-211
• [Journal Article] Intensity-dependent activation of extracellular signal-regulated protein kinases 5 in sensory neurons contributes to pain hypersensitivity (2007)
  • Author(s): Mizushima, T., et. al.
  • Journal Title: J. Pharmacol. Exp. Ther. 321 Pages: 28-34
  • Peer Reviewed
• [Journal Article] Tissue type plasminogen activator induced in rat dorsal horn astrocytes contributes to mechanical hypersensitivity following following dorsal root injury (2007)
  • Author(s): Kozai, T., et. al.
  • Journal Title: Glia 55 Pages: 595-603
  • Peer Reviewed
• [Journal Article] Frequency-dependent ERK phosphorylation in spinal neurons by electric stimulation of the sciatic nerve and the role in electrophysiological activity (2007)
  • Author(s): Fukui, T., et. al.
  • Journal Title: Mol. Pain 3.18
  • Peer Reviewed
• [Journal Article] Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain (2007)
  • Author(s): Dai, Y., et. al.
  • Journal Title: J. Clin. Invest. 117 Pages: 1979-1987
  • Peer Reviewed
• [Journal Article] Activation of extracellular signal-regulated protein kinases 5 in primary afferent neurons contributes to heat and cold hyperalgesia after inflammation (2007)
  • Author(s): Katsura, H., et. al.
  • Journal Title: J. Neurochem. 102 Pages: 1614-1624
  • Peer Reviewed
• [Journal Article] Roles of extracellular signal-regulated protein kinases 5 in spinal microglia and primary sensory neurons for neuropathic pain (2007)
  • Author(s): Obata, K., et. al.
  • Journal Title: J. Neurochem. 102 Pages: 1569-1584
  • Peer Reviewed
• [Journal Article] Activation of fibroblast growth factor receptor by axotomy, through downstream p38 in dorsal root ganglion, contributes to neuropathic pain (2007)
  • Author(s): Yamanaka, H., et. al.
  • Journal Title: Neuroscience 150 Pages: 202-211
  • Peer Reviewed
• [Presentation] Induction of P2Y receptor in the spinal cord following peripheral nerve injury (2008)
  • Author(s): Kobayashi, K., Yamanaka, H., Fukuoka, T. and Noguchi, K
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C., U. S. A
• [Presentation] Induction of P2Y receptor in the spinal cord following peripheral nerve injury (2008)
  • Author(s): Kobayashi, K., et.al.
  • Organizer: The 38th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Washington D.C., U.S.A.
• [Presentation] 神経因性痺痛における脊髄マイクログリアに発現するP2Y12受容体の関与 (2007)
  • Author(s): 小林希実子,福岡哲男,山中博樹,野口光一
  • Organizer: 第29回日本痺痛学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-07-07
• [Presentation] 神経因性疼痛における脊髄マイクログリアに発現するP2Y12受容体の関与. (2007)
  • Author(s): 小林希実子 他
  • Organizer: 第29回日本疼痛学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-07-07
• [Presentation] P2Y12 receptor expressed in spinal microglia contributes to neuropathic pain (2007)
  • Author(s): Kobayashi, K., Fukuoka, T., Yamanaka, H. and Noguchi, K
  • Organizer: 37th Annual Meeting Society for Neuroscience
  • Place of Presentation: San Diego, U.S.A.
• [Presentation] 神経因性痺痛における脊髄マイクログリアに発現するP2Y12受容体の関与 (2007)
  • Author(s): 小林希実子,福岡哲男,山中博樹,野口光一
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] 神経因性疼痛における脊髄マイクログリアに発現するP2Y12受容体の関与. (2007)
  • Author(s): 小林希実子 他
  • Organizer: 第30回日本神経科学大会,
  • Place of Presentation: 横浜
• [Presentation] P2Y12 receptor expressed in spinal microglia contributes to neuropathic pain (2007)
  • Author(s): Kobayashi, K., et. al.
  • Organizer: 37th Annual Meeting Society for Neuroscience
  • Place of Presentation: San Diego, U.S.A