Regulation of activation switching in spinal microglia as a tool of treatment of chronic pain

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19736
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Surgery related to the biological and sensory functions and related fields
• Research Institution: Hyogo Medical University
• Principal Investigator: Noguchi Koichi 兵庫医科大学, 医学部, 学長・教授 (10212127)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 脊髄マイクログリア / 神経障害性疼痛 / IL-4

Outline of Final Research Achievements

Activated microglia in the spinal cord facilitate the hyper-excitability of dorsal horn neurons after peripheral nerve injury via pro-inflammatory molecules. Here, we investigated the possible involvement of the anti-inflammatory cytokine, interleukin-4 (IL-4), in neuropathic pain. We found that nerve injury induced the expression of IL-4Rα mRNA in the spinal cord. A histological analysis revealed that nerve injury induced IL-4Rα mRNA in activated spinal microglia ipsilateral to the injury site. The increases in IL-4R alpha were coincident with the increased expression of phosphorylated STAT6 in spinal microglia. It administration of recombinant IL-4 suppressed mechanical hypersensitivity in neuropathic rats, and the analgesic effect of IL-4 was accompanied by enhancement of pSTAT6 expression in spinal microglia. These results suggest that the adaptive responses of microglia to nerve injury involve both inflammatory and anti-inflammatory signaling, including IL-4R alpha and pSTAT6.

Free Research Field

疼痛基礎医学

Academic Significance and Societal Importance of the Research Achievements

これらの結果は、末梢神経障害後の活性化マイクログリアには、これまで報告されてきた炎症促進性の作用のみならず、炎症抑制性の受容体増加という側面があり、外来性の治療の新しい可能性を示唆したと言える。これらの結果は、グリア関係のトップ雑誌であるGLIAに発表することが出来た。炎症性要素の強い活性化マイクログリアが抗炎症型のM2マイクログリアの機能を示すことが出来たという点に意義が高いと考えられる。