Microglial heterogeneity in chronic pain.

In this review, we report existing preclinical evidence on how the CNS compartment as well as sex affect microglia functions in health. We highlight that recent advances in transcriptomics analyses have led to thorough characterization of disease-associated microglial states in mice and humans. We then consider the specific scenario of peripheral nerve or tissue injury which induce expression of a specific subset of genes in microglia in the dorsal horn of the spinal cord. We suggest the intriguing possibility that future studies may disclose the existence of a unique microglia transcriptional profile that is associated with chronic pain conditions. We also collect evidence that microglial activation in pain-related areas of the brain can be observed in models of neuropathic pain in agreement with recent neuroimaging studies in chronic pain patients. Based on the evidence discussed here, we predict that future studies on the neuroimmune interactions in chronic pain should complement our current understanding of microglia functions, but also adventure in using novel approaches such as scRNA-seq, spatial transcriptomics, CYTOF and transmission electron microscopy to provide a more complete characterization of the function, transcriptome and structure of microglia in chronic pain.