Cellular models of pain: New technologies and their potential to progress preclinical research.
Cellular models of pain: New technologies and their potential to progress preclinical research.
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疼痛的细胞模型：新技术及其进行临床前研究的潜力。
DOI：
10.1016/j.ynpai.2021.100063
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Weir GA
中科院分区：
文献类型：
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作者：
Chrysostomidou L;Cooper AH;Weir GA
人类感觉神经元可以减少止痛药发育过程中的翻译缺口。进入背根神经节(HDRG)神经元的途径正在增加。现在可以通过干细胞技术产生不同的感觉神经元亚型。这些技术的进步将提高我们对人类伤害性感受的理解。体外模型填补了临床前疼痛研究的一个重要领域，允许对分子途径进行详细研究，并在人性化系统的情况下，在体内动物模型和人类患者之间提供转换桥梁。在过去的十年里，基础疼痛研究人员可以使用的细胞技术取得了重大进展，包括开发了区分感觉神经元样细胞和干细胞的方案，以及更多地获得人类背根节组织。在这篇综述中，我们讨论了这两种模型在临床前疼痛研究中的应用：培养皿中的人类感觉神经元能告诉我们什么，而啮齿动物体内的模型不能告诉我们什么？这些模式与它们的内生模式有多相似，我们应该如何评判它们？我们需要考虑哪些限制？我们如何利用细胞模型来提高翻译的成功率？在体外，人类感觉神经元模型为疼痛研究人员提供了研究人类伤害性感受的宝贵工具。如果不断发展，考虑到它们的优点和局限性，并与其他实验策略有效整合，它们可能成为推动疼痛领域进步的动力。
Human sensory neurons can reduce the translational gap in analgesic development. Access to dorsal root ganglion (hDRG) neurons is increasing. Diverse sensory neuron subtypes can now be generated via stem cell technology. Advances of these technologies will improve our understanding of human nociception. In vitro models fill a vital niche in preclinical pain research, allowing detailed study of molecular pathways, and in the case of humanised systems, providing a translational bridge between in vivo animal models and human patients. Significant advances in cellular technology available to basic pain researchers have occurred in the last decade, including developing protocols to differentiate sensory neuron-like cells from stem cells and greater access to human dorsal root ganglion tissue. In this review, we discuss the use of both models in preclinical pain research: What can a human sensory neuron in a dish tell us that rodent in vivo models cannot? How similar are these models to their endogenous counterparts, and how should we judge them? What limitations do we need to consider? How can we leverage cell models to improve translational success? In vitro human sensory neuron models equip pain researchers with a valuable tool to investigate human nociception. With continual development, consideration for their advantages and limitations, and effective integration with other experimental strategies, they could become a driving force for the pain field's advancement.