RhoA/ROCK pathway mediates morphological changes downstream of P2Y12/13 receptors in spinal microglia following peripheral nerve injury

• Project/Area Number: 24500416
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Hyogo Medical University
• Principal Investigator: KOBAYASHI Kimiko 兵庫医科大学, 医学部, 助教 (70418961)
• Co-Investigator(Renkei-kenkyūsha): YAMANAKA Hiroki 兵庫医科大学, 医学部, 講師 (20340995)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マイクログリア / ATP受容体 / MAP kinase / Rho kinase / 脊髄後角 / 神経障害性疼痛 / 形態変化 / ADP / P2Y受容体 / p38 MAPK

Outline of Final Research Achievements

Recent studies have indicated an important role of ATP receptors in spinal microglia, such as P2Y12 or P2Y13, in the development of chronic pain. However, intracellular signaling cascade of these receptors have not been clearly elucidated. We found that P2Y12 and P2Y13 receptors could activate Rho/ROCK and contribute to pathological changes in activated spinal microglia after nerve injury, moreover Rho kinase inhibitor significantly inhibited the injury-induced tactile allodynia.

Research Products

• [Journal Article] RhoA/ROCK pathway mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain. (2015)
  • Author(s): Tatsumi E1, Yamanaka H, Kobayashi K, Yagi H, Sakagami M, Noguchi K.
  • Journal Title: Glia Volume: 63 Issue: 2 Pages: 216-228
  • DOI: 10.1002/glia.22745
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 脊髄microgliaに対するRhoキナーゼ阻害剤の影響と神経障害性疼痛への関与 (2014)
  • Author(s): 山中 博樹, 巽 恵美子, 小林 希実子, 阪上 雅史, 野口 光一
  • Organizer: 第119回日本解剖学会総会全国学術集会
  • Place of Presentation: 自治医科大学
• [Presentation] 脊髄microgliaに対するRhoキナーゼ阻害剤の影響と神経障害性疼痛への関与 (2013)
  • Author(s): 巽 恵美子, 山中 博樹, 小林 希実子, 阪上 雅史, 野口 光一
  • Organizer: 第35回日本疼痛学会
  • Place of Presentation: さいたま市大宮ソニックシティ
• [Presentation] Changes in the expression pattern of P2X receptors in the rat DRG following peripheral nerve injury. (2012)
  • Author(s): Kobayashi K, Yamanaka H, Noguchi K.
  • Organizer: The 42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)
  • Place of Presentation: New Orleans, USA