The Expanding Landscape of Glial Cells in Pain: Mechanisms, Heterogeneity, and Therapeutic Opportunities

Chronic pain conditions remain among the most difficult to treat, and a growing body of evidence identifies glial cells, including astrocytes, microglia, and oligodendrocytes, as active drivers of their onset and persistence rather than passive bystanders. Glial cells shape neuronal excitability, modulate synaptic plasticity, and sustain neuroinflammatory signaling throughout the peripheral and central nervous system, positioning them as central players across a wide range of pain conditions, from neuropathic and inflammatory pain to pain associated with injury, disease, and aging.Recent advances in single-cell and spatial transcriptomics have revealed extraordinary heterogeneity within glial populations. Distinct glial subtypes and activation states emerge depending on pain etiology, disease stage, sex, and anatomical location, challenging the long-standing view of glia as a uniform, reactive population. This heterogeneity helps explain why pain phenotypes and treatment responses vary so widely between individuals and conditions, and it opens new opportunities for mechanism-based interventions, advancing the goal of precision-based medicine.This Research Topic aims to consolidate current understanding of how glial cells contribute to pain, capture the diversity of glial states and responses across different pain conditions, and highlight the therapeutic strategies emerging from this evolving picture. We particularly welcome work that bridges mechanistic insight with translational relevance, helping to define where glia-targeted approaches stand the best chance of reaching the clinic.We welcome contributions addressing, but not limited to:• Molecular and cellular mechanisms of glia-neuron interactions in acute and chronic pain• Glial heterogeneity, subtypes, and cell-state transitions across pain conditions and disease stages• Sex differences and individual variability in glial responses to pain• Circuit-level and systems-level contributions of glia to pain chronification• Novel glia-targeted therapeutic strategies, pharmacological and non-pharmacological• Translational and clinical perspectives on targeting glia for pain management Topic editors: Parisa Gazerani, Marcos Fabio DosSantos, Julie Olson Source: https://www.frontiersin.org/research-topics/85677/the-expanding-landscape-of-glial-cells-in-pain-mechanisms-heterogeneity-and-therapeutic-opportunities