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.
