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深入了解致痛和相关基因表达:开发新型靶向治疗方法的挑战。

Insight into pain-inducing and -related gene expression: a challenge for development of novel targeted therapeutic approaches.

机构信息

Department of Forensic Medicine & Toxicology, Medical School, National & Kapodistrian University of Athens, Athens, Greece.

出版信息

Fundam Clin Pharmacol. 2011 Feb;25(1):48-62. doi: 10.1111/j.1472-8206.2009.00809.x.

Abstract

The multidimensional issue of pain in relation to the need for efficient treatment has been the focus of extensive research. Gaining insight into the molecular mechanisms of pain and identifying specific genes and proteins as possible drug targets is strongly required considering that not all patients can be adequately treated with the currently available drugs. This up-to-date review aimed to summarize the findings of recent proteomic and genomic approaches in different types of pain to comment on their potential role in pain signaling pathways and to evaluate their possible contribution to the development of novel and possibly more targeted pain therapeutic strategies. Although pain treatment strategies have been greatly improved during the past century, no ideal targeted pain treatment has been developed. The development of modern and accurate platforms of technology for the study of genetics and physiology of pain has led to the identification of an increased number of altered genes and proteins that are involved in pain-related pathways. Through genomics and proteomics, pain-related genes and proteins, respectively, may be identified as diagnostic markers or drug targets improving therapeutic strategies. Furthermore, such molecular mediators of pain may reveal novel strategies for individualized pain management. The utilization of unique experimental approaches (through specific animal models) as well as powered genetic association studies conducted on appropriate populations is more than essential.

摘要

多维的疼痛问题与高效治疗的需求一直是广泛研究的焦点。考虑到并非所有患者都能通过现有药物得到充分治疗,深入了解疼痛的分子机制以及确定特定基因和蛋白质作为可能的药物靶点具有重要意义。本篇最新综述旨在总结不同类型疼痛的蛋白质组学和基因组学方法的研究结果,讨论它们在疼痛信号通路中的潜在作用,并评估它们对新型、更具针对性的疼痛治疗策略的可能贡献。尽管在过去一个世纪中,疼痛治疗策略已有了极大的改善,但仍未开发出理想的靶向疼痛治疗方法。用于研究疼痛遗传学和生理学的现代、精确的技术平台的发展,已导致更多与疼痛相关的途径涉及的异常基因和蛋白质的识别。通过基因组学和蛋白质组学,可以分别将与疼痛相关的基因和蛋白质鉴定为改善治疗策略的诊断标志物或药物靶点。此外,这些疼痛的分子介质可能揭示出针对个体化疼痛管理的新策略。利用独特的实验方法(通过特定的动物模型)以及在适当人群中进行的强大的遗传关联研究是至关重要的。

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