Matrix metalloprotease 12 is a novel prospective molecule regulating neuropathic pain

2015 Fiscal Year Final Research Report

• Project/Area Number: 25861397
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: National Center of Neurology and Psychiatry (2015); Wakayama Medical University (2013-2014)
• Principal Investigator: Ujiie Yuka (小林悠佳) 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第五部, 流動研究員 (20511562)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 神経障害性疼痛 / 神経炎症 / マクロファージ / メタロプロテアーゼ

Outline of Final Research Achievements

Neuroinflammation mediated by activated macrophages is important for pathogenesis of neuropathic pain. Here, we investigated the role of MMP12 in neuropathic pain. The gene expression of MMP12 was increased in the injured sciatic nerve (SCN), and MMP12 protein was localized on infiltrating macrophages in the injured site of SCN. By DiI labeling for peripheral blood vessels, DiI leaked into the surrounding tissue after injury, and macrophages accumulated around DiI labeled peripheral vessels. The expression of MMP12 was increased in LPS-activated macrophages. Perineural injection of macrophages depletion agent attenuated nerve injury-induced both tactile allodynia and thermal hyperalgesia, and suppressed the mRNA expressions of MMP12 and inflammatory cytokines. Furthermore, perineural injection of MMP12 specific inhibitor also suppressed tactile allodynia and thermal hyperalgesia. Taken together, MMP12 derived from macrophages acts as an exacerbating factor of neuropathic pain.

Free Research Field

薬理学