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超越单一靶点：利用钠通道的简并性实现骨关节炎镇痛

Beyond single targets: leveraging degeneracy in sodium channels for osteoarthritis analgesia.

作者信息

Perez-Miller Samantha, Khanna Rajesh

机构信息

Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL, USA.

Center for Advanced Pain Therapeutics and Research (CAPToR), College of Medicine, University of Florida, Gainesville, FL, USA.

出版信息

Pain Rep. 2025 May 27;10(4):e1289. doi: 10.1097/PR9.0000000000001289. eCollection 2025 Aug.

DOI:10.1097/PR9.0000000000001289
PMID:40444024
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12119048/
Abstract

Shin SM, Itson-Zoske B, Xu H, Xiang H, Fan F, Hogan QH, Yu H. Sensory neuron-specific block of multifaceted sodium channels mitigates neuropathic pain behaviors of osteoarthritis. Pain Rep 2025. DOI: 10.1097/PR9.0000000000001288.

摘要

申SM、伊特森 - 佐斯克B、徐H、向H、范F、霍根QH、于H。多方面钠通道的感觉神经元特异性阻断减轻骨关节炎的神经性疼痛行为。疼痛报告2025年。DOI: 10.1097/PR9.0000000000001288

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7faf/12119048/21e3ec4af255/painreports-10-e1289-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7faf/12119048/6589c43ec6d9/painreports-10-e1289-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7faf/12119048/21e3ec4af255/painreports-10-e1289-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7faf/12119048/6589c43ec6d9/painreports-10-e1289-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7faf/12119048/21e3ec4af255/painreports-10-e1289-g002.jpg

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Beyond single targets: leveraging degeneracy in sodium channels for osteoarthritis analgesia.超越单一靶点：利用钠通道的简并性实现骨关节炎镇痛
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Sensory neuron-specific block of multifaceted sodium channels mitigates neuropathic pain behaviors of osteoarthritis.多面钠通道的感觉神经元特异性阻断减轻骨关节炎的神经性疼痛行为。
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本文引用的文献

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Voltage-gated sodium channels in excitable cells as drug targets.可兴奋细胞中的电压门控钠通道作为药物靶点。
Nat Rev Drug Discov. 2025 May;24(5):358-378. doi: 10.1038/s41573-024-01108-x. Epub 2025 Feb 3.
2
Dorsal root ganglion toxicity after AAV intra-CSF delivery of a RNAi expression construct into non-human primates and mice.在非人灵长类动物和小鼠的脑脊液中注射携带RNAi表达构建体的腺相关病毒（AAV）后出现的背根神经节毒性。
Mol Ther. 2025 Jan 8;33(1):215-234. doi: 10.1016/j.ymthe.2024.11.029. Epub 2024 Nov 19.
3
Uncoupling the CRMP2-Ca2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model.
解偶联 CRMP2-Ca2.2 相互作用可减少临床前关节痛模型中的疼痛样行为。
J Pain. 2024 Dec;25(12):104664. doi: 10.1016/j.jpain.2024.104664. Epub 2024 Sep 2.
4
Small molecule targeting Na V 1.7 via inhibition of CRMP2-Ubc9 interaction reduces pain-related outcomes in a rodent osteoarthritic model.通过抑制CRMP2-Ubc9相互作用靶向Nav1.7的小分子可减轻啮齿动物骨关节炎模型中与疼痛相关的症状。
Pain. 2025 Jan 1;166(1):99-111. doi: 10.1097/j.pain.0000000000003357. Epub 2024 Jul 26.
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Recent advances in small molecule Nav 1.7 inhibitors for cancer pain management.小分子 Nav1.7 抑制剂在癌症疼痛管理中的最新进展。
Bioorg Chem. 2024 Sep;150:107605. doi: 10.1016/j.bioorg.2024.107605. Epub 2024 Jun 29.
6
Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders.紊乱但有效：短线性基序作为过度兴奋障碍的基因治疗靶点。
J Clin Invest. 2024 Jul 1;134(13):e182198. doi: 10.1172/JCI182198.
7
Peripherally targeted analgesia via AAV-mediated sensory neuron-specific inhibition of multiple pronociceptive sodium channels.通过 AAV 介导的感觉神经元特异性抑制多种致痛性钠离子通道实现外周靶向镇痛。
J Clin Invest. 2024 May 9;134(13):e170813. doi: 10.1172/JCI170813.
8
Similar excitability through different sodium channels and implications for the analgesic efficacy of selective drugs.通过不同的钠通道产生相似的兴奋性及其对选择性药物镇痛效果的影响。
Elife. 2024 Apr 30;12:RP90960. doi: 10.7554/eLife.90960.
9
Na1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis.作为软骨细胞调节剂和骨关节炎治疗靶点的 Na1.7。
Nature. 2024 Jan;625(7995):557-565. doi: 10.1038/s41586-023-06888-7. Epub 2024 Jan 3.
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Proc Natl Acad Sci U S A. 2023 Nov 21;120(47):e2305215120. doi: 10.1073/pnas.2305215120. Epub 2023 Nov 16.