Emerging Roles of Glial Cells in Neuropathic Pain: From Cell Biology to Innovative Treatment Strategies

Neuropathic pain, a chronic condition resulting from nervous system lesions or diseases, remains a formidable clinical challenge due to its complex and refractory nature. Historically, research has been predominantly neuron-centric. However, a paradigm shift is underway, highlighting glial cells—astrocytes, microglia, oligodendrocyte precursor cells (OPC) or NG2 glia, oligodendrocytes and Schwann cells—as critical active participants in the pathogenesis of neuropathic pain. Upon nerve injury, these non-neuronal cells become activated, initiating neuroinflammatory cascades that drive central sensitization and maladaptive plasticity, thereby chronicifying pain. Their dynamic interactions with neurons and immune cells modulate the microenvironment, influencing processes like axonal regrowth, remyelination, synaptic remodeling and neural circuit reorganization. While a critical gap persists in understanding the precise molecular mechanisms by which glial cells regulate neuropathic pain.

While their involvement is established, the specific signaling pathways, phenotypic shifts, and crosstalk between glial subtypes and neurons that initially drive maladaptive plasticity remain poorly defined. This knowledge deficit hinders the development of targeted therapies that can selectively suppress pro-nociceptive glial functions. To bridge this gap, this Research Topic will compile cutting-edge research that: 1) Deciphers the dynamic temporal and spatial regulation of glial activation states and elucidates novel glia-derived mediators and their mechanisms of action, 2) Seeks to explore these emerging, multifaceted roles of glia, bridging their contributions from pain occurrence, persistence to pain resolution in molecular, cellular, synaptic, circuit, and behavioral levels, especially in an integrative perspective, and 3) Explores innovative strategies, such as glia-specific neuromodulation or targeted drug delivery, to resolve pain.

We welcome submissions of original articles providing novel insights into either the mechanisms underlying pain, or new therapeutic strategies and targets for any potential treatment of pain. We also encourage submissions of review articles that summarize current knowledge or provide insightful perspectives regarding neuropathic pain that explore specific themes, including:

1) Molecular mechanisms of glial activation (microglia, astrocytes, OPC or NG2 glia, oligodendrocytes, Schwann cells) in neuropathic pain.
2) Glia-mediated neuroimmune interactions and central sensitization.
3) The role of glia in regulating synaptic plasticity, circuitry, and pain behavior.
4) Pro-regenerative glial functions, including axonal guidance, remyelination, and scar resolution during pain occurrence, persistence and resolution.
5) Novel therapeutic strategies targeting specific glial pathways or phenotypes to alleviate pain.

By bringing together diverse perspectives, this collection will provide a comprehensive view of glial biology, paving the way for transformative treatments for neuropathic pain.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Glial Cells, Neuropathic Pain, Cell Biology，Treatment Strategies，Astrocytes, Microglia, Oligodendrocyte precursor cells (OPC), NG2 glia, Oligodendrocytes, Schwann cells

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.