Analysis of pain hypersensitivity due to the mTOR mediated proteome alteration in the primary afferent neurons.

• Project/Area Number: 23592306
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: AMAYA Fumimasa 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60347466)
• Co-Investigator(Kenkyū-buntansha): SAWA Teiji 京都府立医科大学, 医学研究科, 教授 (10206013)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 痛覚過敏 / mTOR / IGF / 一次知覚神経 / 組織損傷 / VGLUT2

Outline of Final Research Achievements

Phosphorylated mTOR (pmTOR) expression was detected in the primary afferent neurons in the dorsal root ganglion (DRG). Expression of pmTOR increased after plantar incision. mTOR inhibitor rapamycin reduced plantar incision-induced hyperalgesia. Intralpantar injection of IGF increased pmTOR expression and IGF inhibitor inhibited plantar incision-induced pmTOR induction. VGLUT3 expression was increased in the DRG after the plantar incision and rapamycin prevented incision-induced VGLUT-3 increase. IGF injection into the paw increased VGLUT-3 expression in the DRG.
These results demonstrated that increased local production of IGF facilitates mTOR phosphorylation and increase VGLUT3 expression in the DRG neurons, leading pain hypersensitivity after the tissue injury.

Research Products

• [Journal Article] Tumor necrosis factor-alpha induces expression of C/EBP-beta in primary afferent neurons following nerve injury. (2014)
  • Author(s): Sasaki M, Hashimoto S, Sawa T, Amaya F
  • Journal Title: Neuroscience Volume: 279 Pages: 1-9
  • DOI: 10.1016/j.neuroscience.2014.08.032
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tissue injury and related mediators of pain exacerbation. (2013)
  • Author(s): Amaya F, Izumi Y, Matsuda M and Sasaki M.
  • Journal Title: Current Neuropharmacology Volume: 11 Issue: 6 Pages: 592-597
  • DOI: 10.2174/1570159x11311060003
  • Peer Reviewed
• [Journal Article] Activation of p38 mitogen-activated protein kinase in the dorsal root ganglion contributes to pain hypersensitivity after plantar incision (2013)
  • Author(s): Mizukoshi K, Sasaki M, Izumi Y, Miura M, Watanabe M, Amaya F
  • Journal Title: Neuroscience Volume: 234 Pages: 77-87
  • DOI: 10.1016/j.neuroscience.2013.01.001
  • Peer Reviewed
• [Journal Article] ransient paraplegia after accidental insertion of an epidural catheter into an arachnoid cyst. (2011)
  • Author(s): Oku H, Sawa T, Saito A, Amaya F
  • Journal Title: Reg Anesth Pain Med Volume: 56 Issue: 5 Pages: 524-525
  • DOI: 10.1097/aap.0b013e318228cf00
  • Peer Reviewed
• [Journal Article] Peripheral sensitization caused by insulin-like growth factor 1 contributes to pain hypersensitivity after tissue injury (2011)
  • Author(s): Miura M, Sasaki M, Mizukoshi K, Shibasaki M, Izumi Y, Shimosato G, Amaya F
  • Journal Title: PAIN Volume: 152(4) Issue: 4 Pages: 888-895
  • DOI: 10.1016/j.pain.2011.01.004
  • Peer Reviewed
• [Presentation] Phosphorylation of mTOR maintains pain hypersensitivity after the tissue injury (2014)
  • Author(s): Y. Izumi, Sasaki M, Amaya F
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington DC
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Nerve injury increases cAMP sensor Epac1 and Epac2 in the distinct subgroups of DRG neurons. (2014)
  • Author(s): Matsuda M, Yamakita S, Yamaguchi Y, Izumi Y Amaya F.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington DC
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] 手術後痛は本当に取るべきなのか？ 創傷治癒と痛み：創傷部の末梢神経に何が起こるか？ (2013)
  • Author(s): 天谷文昌
  • Organizer: 第50回日本麻酔科学会学術集会
  • Place of Presentation: 札幌
  • Invited
• [Presentation] TNF-alphaはp38MAPKを介して術後疼痛の成立に寄与する (2012)
  • Author(s): 水越圭子、佐々木美佳、和泉勇太、天谷文昌
  • Organizer: 第34回日本疼痛学会
  • Place of Presentation: 熊本
• [Presentation] 一次知覚神経におけるmTORは術後痛モデルの痛覚過敏に関与する (2012)
  • Author(s): 和泉勇太、水越圭子、佐々木美佳、天谷文昌
  • Organizer: 第34回日本疼痛学会
  • Place of Presentation: 熊本
• [Presentation] 良質な術後痛治療をめざして：Peripheral sensitizationのメカニズムと制御 (2011)
  • Author(s): 天谷文昌
  • Organizer: 日本麻酔科学会第58回学術集会(招待講演)
  • Place of Presentation: 神戸