Burke Nikita N, Fan Churmy Y, Trang Tuan
Department of Comparative Biology and Experimental Medicine, Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Exp Physiol. 2016 Aug 1;101(8):1003-21. doi: 10.1113/EP085714.
What is the topic of this review? This review discusses the origins and development of microglia, and how stress, pain or inflammation in early life disturbs microglial function during critical developmental periods, leading to altered pain sensitivity and/or increased risk of chronic pain in later life. What advances does it highlight? We highlight recent advances in understanding how disrupted microglial function impacts the developing nervous system and the consequences for pain processing and susceptibility for development of chronic pain in later life. The discovery of microglia is accredited to Pío del Río-Hortega, who recognized this 'third element' of CNS cells as being morphologically distinct from neurons and astrocytes. For decades after this finding, microglia were altogether ignored or relegated as simply being support cells. Emerging from virtual obscurity, microglia have now gained notoriety as immune cells that assume a leading role in the development, maintenance and protection of a healthy CNS. Pioneering studies have recently shed light on the origins of microglia, their role in the developing nervous system and the complex roles they play beyond the immune response. These studies reveal that altered microglial function can have a profoundly negative impact on the developing brain and may be a determinant in a range of neurodevelopmental disorders and neurodegenerative diseases. The realization that aberrant microglial function also critically underlies chronic pain, a debilitating disorder that afflicts over 1.5 billion people worldwide, was a major conceptual leap forward in the pain field. Adding to this advance is emerging evidence that early life noxious experiences can have a long-lasting impact on central pain processing and adult pain sensitivity. With microglia now coming of age, in this review we examine the association between adverse early life events, such as stress, injury or inflammation, and the influence of sex differences, on the role of microglia in pain physiology in adulthood.
这篇综述的主题是什么？本综述讨论了小胶质细胞的起源与发育，以及生命早期的压力、疼痛或炎症如何在关键发育阶段扰乱小胶质细胞功能，导致后期疼痛敏感性改变和/或慢性疼痛风险增加。它突出了哪些进展？我们重点介绍了在理解小胶质细胞功能紊乱如何影响发育中的神经系统以及对后期疼痛处理和慢性疼痛易感性的后果方面的最新进展。小胶质细胞的发现归功于皮奥·德尔·里奥 - 奥尔特加，他认识到中枢神经系统细胞的这种“第三种元素”在形态上与神经元和星形胶质细胞不同。在这一发现后的几十年里，小胶质细胞完全被忽视或仅仅被视为支持细胞。小胶质细胞从几乎默默无闻中崛起，如今已声名远扬，成为在健康中枢神经系统的发育、维持和保护中起主导作用的免疫细胞。开创性研究最近揭示了小胶质细胞的起源、它们在发育中的神经系统中的作用以及它们在免疫反应之外所起的复杂作用。这些研究表明，小胶质细胞功能改变可能对发育中的大脑产生深远的负面影响，并且可能是一系列神经发育障碍和神经退行性疾病的一个决定因素。认识到异常的小胶质细胞功能也是慢性疼痛的关键基础，慢性疼痛是一种使全球超过15亿人受苦的衰弱性疾病，这是疼痛领域的一个重大概念性飞跃。进一步的进展是，越来越多的证据表明，生命早期的有害经历会对中枢疼痛处理和成人疼痛敏感性产生长期影响。随着小胶质细胞如今逐渐成熟，在本综述中，我们研究了诸如压力、损伤或炎症等不良早期生活事件与性别差异的影响之间的关联，以及它们对成年期小胶质细胞在疼痛生理学中的作用的影响。
