Novel therapy for neuropathic pain model based on mRNA agerts
| Project/Area Number |
20K09455
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Hirai Takashi 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (40510350)
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| Co-Investigator(Kenkyū-buntansha) |
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)
吉井 俊貴 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (50583754)
位高 啓史 東京医科歯科大学, 生体材料工学研究所, 教授 (60292926)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 神経障害性疼痛 / 脊髄後角 / RNAシーケンス / ナノミセル / 脊髄ミクログリア / 後根神経節 / 絞扼性神経モデル |
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| Outline of Research at the Start |
絞扼性神経障害モデルである、4種類の疼痛モデルを作成し、それぞれの脊髄後角における遺伝子変化を次世代シーケンサーで解析、今まで明らかにされてこなかった共通する遺伝子変化を明らかにする。さらに神経障害性疼痛モデルの脊髄後角で共通して変化する遺伝子を適正化させ、疼痛を緩和できるかを検討する。これにはポリエチレングリコールとポリカチオンにより合成された共重合体（ナノミセル）をキャリアとして用い標的遺伝子mRNAを創生し脊髄後角へデリバリーさせることで、いままでになかった疼痛制御を目指す。
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| Outline of Final Research Achievements |
We created a mouse neuropathic pain model, excised the dorsal horn of the spinal cord, extracted RNA, and comprehensively investigated gene expression changes using a next-generation sequencer. Approximately 70 types of RNAseq for the dorsal horn of the spinal cord showed changes in expression between the affected side and the Sham model. Of these, 6 genes were upregulated in the SNI model, and these were named genes A to F, respectively. The expression level of gene A was significantly elevated with a difference of about 8000-fold. In addition, the expression level of gene A increased 2.8-fold on the affected side in a comparison of the unaffected side and the affected side in the SNI model. Genes B and F were also significantly elevated in the affected side of the SNI model. On the other hand, it was also found that the expression of about 60 kinds of genes was decreased.
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| Academic Significance and Societal Importance of the Research Achievements |
末梢神経障害が生じることで脊髄後角において患側では多くの遺伝子発現が低下することが分かったが、少数の遺伝子では劇的に発現が増加することが分かった。様々な神経障害モデルにおける共通の遺伝子変化を抽出し、メカニズムの原因を突き止めることができれば新たな治療標的として期待できると考えられた。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Usefulness of lysophosphatidylcholine measurement in the cerebrospinal fluid for differential diagnosis of neuropathic pain: Possible introduction into clinical laboratory testing.2023
Author(s)
Kurano M, Sumitani M, Akiyama Y, Yamada M, Fujimura D, Yamaki S, Kano K, Aoki J, Hayakawa K, Takahashi T, Hirai T, Okawa A, Kume H, Ogata T, Tanaka S, Chikuda H, Yatomi Y.
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Journal Title
Clin Chim Acta.
Volume: 15;541
Pages: 117249-117249
DOI
Related Report
Peer Reviewed
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[Journal Article] Systemic DNA/RNA heteroduplex oligonucleotide administration for regulating the gene expression of dorsal root ganglion and sciatic nerve.2022
Author(s)
Kaburagi H, Nagata T, Enomoto M, Hirai T, Ohyagi M, Ihara K, Yoshida-Tanaka K, Ebihara S, Asada K, Yokoyama H, Okawa A, Yokota T.
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Journal Title
Mol. Ther. Nucleic. Acids.
Volume: 6
Pages: 910-919
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical Characteristics of Patients with Ossification of the Posterior Longitudinal Ligament and a High OP Index: A Multicenter Cross-Sectional Study (JOSL Study)2022
Author(s)
Hirai T, Yoshii T, Hashimoto J, Ushio S, Mori K, Maki S, Katsumi K, Nagoshi N, Takeuchi K, Furuya T, Watanabe K, Nishida N, Nishimura S, Watanabe K, Kaito T, Kato S, Nagashima K, Koda M, Nakashima H, Imagama S, er al.
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Journal Title
Journal of Clinical Medicine
Volume: 11
Issue: 13
Pages: 3694-3694
DOI
Related Report
Peer Reviewed / Open Access
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