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疼痛基因

Pain genes.

作者信息

Foulkes Tom, Wood John N

机构信息

Department of Stem Cell Biology and Developmental Genetics, National Institute for Medical Research, London, United Kingdom.

出版信息

PLoS Genet. 2008 Jul 25;4(7):e1000086. doi: 10.1371/journal.pgen.1000086.

Abstract

Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors) signal the existence of tissue damage to the central nervous system (CNS), where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

摘要

疼痛在任何时候都困扰着多达20%的人群,它既带来了巨大的治疗挑战,也是理解神经系统机制的一条途径。专门的感觉神经元(伤害感受器)向中枢神经系统(CNS)发出组织损伤存在的信号,在中枢神经系统中,疼痛通过涉及许多中枢神经系统结构的复杂网络来体现。利用模式生物研究疼痛通路的遗传学方法已经确定了传感器的分子性质、改变神经元活动所涉及的调节机制,以及免疫系统细胞在驱动疼痛通路中的关键作用。在人类中,对人类疼痛突变体的图谱分析以及对疼痛行为改变的双胞胎研究和关联研究已经确定了疼痛系统的重要调节因子。反过来,慢性疼痛治疗的新药物靶点已经在转基因小鼠研究中得到验证。因此,疼痛通路的遗传学研究补充了传统的神经科学方法,如电生理学和药理学,使我们对疼痛感知的分子基础有了新的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9696/2432024/960f9f1360d9/pgen.1000086.g001.jpg

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