Omics approaches to discover pathophysiological pathways contributing to human pain.

Omics approaches to discover pathophysiological pathways contributing to human pain.
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DOI:
10.1097/j.pain.0000000000002726
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发表时间:
2022-11-01
期刊:
影响因子:
7.4
通讯作者:
--
中科院分区:
医学1区
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--
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存在有限的数据来告知慢性疼痛的基于机制的理解和管理,因此,存在明显未满足的需求,以更好地定义疼痛的分子机制,以开发新的治疗策略。使用人类队列生成关于疼痛状态的分子病理生理学的知识比动物模型具有明显的优势,并且可以使用分子和细胞全基因组方法在已表征不同疼痛状态和不同疼痛相关中间表型的队列中实现。至关重要的是,这种方法是无假设的,因此既启发式又导致对数据的无偏见解释,不受特定假设或基因候选者的限制或通过特定假设或基因候选者进行漏斗式分析。最近在无偏分子筛选方法和分析工具的开发方面取得了巨大进展。67这些多组学方法包括以高通量、全面的方式对DNA、RNA、蛋白质和小分子进行分子分析。它们的使用已经推进甚至改变了我们对许多疾病的病理生理学的理解,包括中风、糖尿病和癌症。27重要的是,组学方法允许系统地使用和整合多个数据集,在解释结果时创造更多的维度,从而导致新的概念方法和治疗策略的发展。
There exist limited data to inform mechanism-based understanding and management of chronic pain, and thus, there is a clear unmet need to better define the molecular mechanisms of pain to develop novel treatment strategies. Generating knowledge regarding molecular pathophysiology of pain states using human cohorts has an obvious advantage over animal models, and it can be achieved using molecular and cellular genome-wide approaches in cohorts that have been characterized for different pain states and different painrelated intermediate phenotypes. Crucially, such approaches are hypothesis free, and thus both heuristic and resulting in the unbiased interpretation of data, not restricted by or funneled through specific hypotheses or gene candidates. There has been tremendous progress lately in the development of unbiased molecular screening approaches and analytic tools. 67 These multiomics approaches include molecular assays of DNA, RNA, proteins, and small molecules in a high-throughput, comprehensive manner. Their use has advanced and even changed our understanding of the pathophysiology of many diseases, including stroke, diabetes, and cancer. 27 Importantly,-omics approaches permit the systematic use and integration of multiple data sets, creating further dimensionality in the interpretation of the results that can lead to the development of new conceptual approaches and treatment strategies.
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