Price Theodore J, Melemedjian Ohannes K
Department of Pharmacology, The University of Arizona School of Medicine, Tucson, AZ, USA.
Results Probl Cell Differ. 2012;54:41-59. doi: 10.1007/978-3-642-21649-7_4.
The purpose of this chapter is to discuss the role of the fragile X mental retardation protein (FMRP) in the spinal sensory system and the potential for use of the mouse model of fragile X syndrome to better understand some aspects of the human syndrome as well as advance knowledge in other areas of investigation, such as pain amplification, an important aspect of clinical pain disorders. We describe how the Fmr1 knockout mouse can be used to better understand the role of Fmrp in axons using cultures of sensory neurons and using manipulations to these neurons in vivo. We also discuss the established evidence for a role of Fmrp in nociceptive sensitization and how this evidence relates to an emerging role of translation control as a key process in pain amplification. Finally, we explore opportunities centered on the Fmr1 KO mouse for gaining further insight into the role of translation control in pain amplification and how this model may be used to identify novel therapeutic targets. We conclude that the study of the spinal sensory system in the Fmr1 KO mouse presents several unique prospects for gaining better insight into the human disorder and other clinical issues, such as chronic pain disorders, that affect millions of people worldwide.
本章的目的是讨论脆性X智力低下蛋白(FMRP)在脊髓感觉系统中的作用,以及利用脆性X综合征小鼠模型更好地理解人类综合征某些方面的潜力,并推动在其他研究领域的知识进展,例如疼痛放大,这是临床疼痛障碍的一个重要方面。我们描述了如何使用Fmr1基因敲除小鼠,通过感觉神经元培养以及在体内对这些神经元进行操作,来更好地理解Fmrp在轴突中的作用。我们还讨论了Fmrp在伤害性感受敏化中作用的现有证据,以及该证据如何与翻译控制作为疼痛放大关键过程的新作用相关。最后,我们探索了以Fmr1基因敲除小鼠为中心的机会,以进一步深入了解翻译控制在疼痛放大中的作用,以及该模型如何用于识别新的治疗靶点。我们得出结论,对Fmr1基因敲除小鼠脊髓感觉系统的研究为更好地理解人类疾病以及影响全球数百万人的其他临床问题(如慢性疼痛障碍)提供了几个独特的前景。