2023 Fiscal Year Final Research Report
Elucidation of infantile episodic limb pain mechanism induced by cold exposure
| Project/Area Number |
21K10394
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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 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | Kyoto Prefectural University of Medicine (2023)
Kyoto University (2021-2022) |
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Principal Investigator |
Okuda Hiroko 京都府立医科大学, 医学部, 研究員 (30709663)
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| Co-Investigator(Kenkyū-buntansha) |
S Youssefian 京都大学, 医学研究科, 教授 (00210576)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 小児四肢疼痛発作症 / 疼痛 / 寒冷 / ＳＣＮ11Ａ / ＳＣＮ10Ａ |
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| Outline of Final Research Achievements |
It has been shown that the cause of familial episodic pain syndrome is some mutations in the SCN11A，which encoding one of sodium channel subtype Nav1.9. Mutations of Nav1.9 contribute the repetitive firing, which induces the hypersensitivity of pain. Nav1.9 and Nav1.8 are component of the action potential of pain pathway, therefore, we investigated changes in Nav1.8 and Nav1.9 mutation expression and cooperative relationships in action potentials.
We tried the immunohistochemistry of Nav1.8 and Nav1.9 (WT and p. R222S mutation) and are in the process of trying to determine the antibody cross reactivity. While we tried to investigate the effects of the novel inhibitor, which has the effects on Nav1.7, 1.8, and 1.9 on mice harboring p. R222S mutation. This drug was reduced the pain response to pain induced by cold exposure behavioral tests, and also suppressed the repetitive firing of pain pathway of these mutant mice.
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| Free Research Field |
生理学
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| Academic Significance and Societal Importance of the Research Achievements |
「小児四肢疼痛発作症」は、寒冷による疼痛増悪という特徴を持つ。この特徴はモデルマウスでも再現され、本特徴を解析することは疾患患者の疼痛緩和、薬剤開発につながると考えた。疼痛経路に発現するナトリウムチャネル亜型であるNav1.9原因変異とともに疼痛伝達に関与するNav1.8の相互作用を検討したが、抗体交差性について引き続き検討の余地がある。一方でNav1.7-1.9を阻害する新規疼痛阻害薬の薬効を本疾患モデルマウスで調べたところ、寒冷暴露による疼痛行動、および疼痛経路の神経活動の過興奮が抑えられた。よって寒冷暴露による患者の発作性疼痛増悪は本薬剤で抑制される可能性を示唆した。
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