Skin-derived glial-like cell transplantation therapy for intractable pain

• Project/Area Number: 17K16718
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Tohoku University
• Principal Investigator: Murakami Toru 東北大学, 大学病院, 助教 (90756248)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 神経障害性胃痛 / 動物モデル / 細胞移植 / 神経障害性痛 / 神経再生 / 疼痛管理学

Outline of Final Research Achievements

We first established a rat model for the judgement of cell transplantation therapies. Drugs for neuropathic pain were effective in rats with their left sciatic nerve pinched at fixed constant pressure, whereas NSAIDs were ineffective. The rats showed motor function decline represented by Sciatic Function Index from one day to two weeks after surgery. Immunohistochemistry using clipped site of sciatic nerve and dorsal root ganglia showed the evidence of axonopathy and demyelination. Although rat Schwann cells transplantation into injured sites were not clearly effective, statistically significant relief of hyperalgesia was observed with the stronger clip pressure.
Above results indicated the possibility of cell transplantation therapies for neuropathic pain.

Academic Significance and Societal Importance of the Research Achievements

神経障害性痛は先進国で1～7%、本邦で600万人の患者が存在するとされており、著しいQOL低下が長期間持続し国家の経済にも無視できない負荷を与えていると言われている。治療は薬物療法、運動療法、神経ブロックなどが行われるが、いずれも現時点では根治的な治療法とはなっていない。本研究で確立したラット神経障害性痛モデルは、①実際の神経障害性痛の病態に近い、②体内に異物が残らないため神経障害部位に直接働きかける治療法の開発に使用可能である、という特徴があり、さらに神経再生に主要な役割を果たすシュワン細胞投与の効果が確認され始めていることから、本症候群の新たな根治的治療法の開発につながる可能性がある。

Research Products

• [Journal Article] Direct conversion of adult human skin fibroblasts into functional Schwann cells that achieve robust recovery of the severed peripheral nerve in rats. (2019)
  • Author(s): Kitada M, Murakami T, Wakao S, Li G, Dezawa M
  • Journal Title: Glia Volume: 67(5) Issue: 5 Pages: 950-966
  • DOI: 10.1002/glia.23582
  • Peer Reviewed
• [Presentation] A novel rat model of neuropathic pain established by clamping the sciatic nerve shows mechanical allodynia and microglial hyperplasia in the spinal cord (2018)
  • Author(s): Michio Kumagai, Toru Murakami, Masanori Yamauchi, Hideaki Obata
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Presentation] 末梢性神経障害性痛に対する神経再生療法に向けたラットモデルの開発 (2018)
  • Author(s): 熊谷道雄，村上徹，山内正憲
  • Organizer: 日本疼痛学会
• [Presentation] A Novel Rat Model of Neuropathic Pain by Clamping the Sciatic Nerve for Cell Transplantation (2017)
  • Author(s): Michio Kumagai, Toru Murakami, Hideaki Obata, Shigekazu Sugino, Masanori Yamauchi
  • Organizer: ANESTHESIOLOGY 2017
  • Int'l Joint Research