Establishment of treatment by regeneration and suppressing degeneration in human intervertebral disc.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10816
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Toyama
• Principal Investigator: SEKI Shoji 富山大学, 大学院医学薬学研究部(医学), 助教 (00432112)
• Co-Investigator(Kenkyū-buntansha): 川口 善治 富山大学, 大学院医学薬学研究部(医学), 准教授 (00262527) ; 箭原 康人 富山大学, 附属病院, 医員 (60456390)
• Research Collaborator: NOGAMI makiko ; MAKINO hiroto
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: AP-1阻害剤 / 腰椎椎間板 / 椎間板穿刺モデル / 腰痛症

Outline of Final Research Achievements

Lumbar intervertebral disc (IVD) degeneration is attributable mainly to LBP, called discogenic pain, which often leads to disc herniation presenting as sciatica. We investigated the effects of inhibition of c-Fos/AP-1（T-5224）on IVD degeneration and associated pain. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of x-ray, MRI findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. T-5224 prevented disc degeneration, and oral administration of T-5224 extended the tail flick latency as a measure of heat stimulation in the rat tail-puncture model. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain.

Free Research Field

脊椎椎間板、脊椎疾患、遺伝子解析

Academic Significance and Societal Importance of the Research Achievements

腰椎椎間板変性は、脊柱管狭窄症、ヘルニア、腰痛の原因の一つである。これらの疾患は若年-中高年まで労働生産性の高い年代に患うことが多い。現在臨床応用可能な椎間板変性抑制の薬はなく、早期臨床応用可能な治療法の開発は急務である。椎間変性が抑制できれば、多くの腰痛や狭窄症に悩む患者にとって非常に朗報である。c-fos/AP-1阻害薬（T-5224）は、動物実験レベルでは椎間板変性抑制作用とその関連痛を抑制した。この薬は実際にヒトへの投与も可能であり、実際に臨床的効果が得られれば、労働生産性の向上など社会的利益も大きい点で、極めて有益な研究であると確信する。