2022 Fiscal Year Final Research Report

Therapeutic development and role of non-neuronal cells in dorsal root ganglion for neuropathic pain

Research Project

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Project/Area Number	19K09543
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56020:Orthopedics-related
Research Institution	Tokyo Medical and Dental University
Principal Investigator	Enomoto Mitsuhiro 東京医科歯科大学, 東京医科歯科大学病院, 非常勤講師 (90451971)
Co-Investigator(Kenkyū-buntansha)	辻邦和東京医科歯科大学, 大学院医歯学総合研究科, ジョイントリサーチ講座教授 (20323694) 大川淳東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30251507) 平井高志東京医科歯科大学, 大学院医歯学総合研究科, 講師 (40510350)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	神経障害性疼痛 / 末梢神経障害 / 後根神経節
Outline of Final Research Achievements	Spared nerve injury (SNI) model exhibits strong mechanical hypersensitivity in the sural nerve dominant area. Wild-type mice were used and neuron, satellite cell (SGC), and microglia in lumbar DRGs were histologically analyzed 1, 3 and 6 weeks after SNI. The number of neuron decreased 1 week and maintained up to 6 weeks after SNI. In contrast, the number of SGC showed an increase 1 week and stepwise decline 6 weeks after SNI. The number of microglia also showed an increase and then decreased 3 weeks after SNI. The activation of SGC maintained for 6 weeks. These results indicate that SGC would induce prolonged painful states after nerve injury. Further analyses are needed for gene profiles such as ion channels between neuron and non-neuronal cell. Finally, systemic administration of heteroduplex oligonucleotide (HDO) significantly inhibited gene expression in DRGs. A therapy with HDO may be a clinically effective approach to modify gene expressions of DRGs for chronic neuropathic pain.
Free Research Field	整形外科学
Academic Significance and Societal Importance of the Research Achievements	脊椎変性疾患や絞扼性末梢神経障害を有していると「神経痛」を訴えることが多く、治療に難渋する。本研究目的は、神経伝達経路の後根神経節（DRG）で慢性疼痛に関与する細胞、分子を探索し、新規治療の開発を行うことである。本研究期間では、DRG内の神経細胞と非神経細胞であるグリアが密接に関与し、疼痛の慢性化に寄与することが明らかになった。さらに新規核酸医薬HDOの静脈注射によってDRGの遺伝子制御が可能となった。今後、DRGを標的としたHDOによる遺伝子制御によって「神経痛」の克服を目指す。