ArticlePain research & management2026
Dissection of Microglial Heterogeneity and Identification of Pain-Related Subpopulations After Traumatic Brain Injury.
Article in Pain research & management, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPain following traumatic brain injury (TBI) is a major challenge in clinical management. Neuroinflammatory responses, particularly those involving microglia, are increasingly implicated in the synaptic and circuit-level remodeling associated with post-TBI pain. However, the conventional M1/M2 framework does not adequately capture the temporal and functional diversity of microglial states after injury. This study aimed to characterize microglial heterogeneity and identify specific microglial subpopulations potentially associated with post-TBI pain-related neural remodeling.
methodsWe reanalyzed the publicly available single-cell RNA sequencing dataset GSE226207, which comprised intact cortical samples and cortical samples collected at 3 and 5 days after cortical stab-wound injury from control and inhibitor-treated mice. The inhibitor-treated groups received combined pharmacological inhibition of the CXCR3 and TLR1/2 pathways. Seurat was used for data processing, clustering, cell-type annotation, and microglial subclustering. AUCell was applied to evaluate inflammatory-, repair-, and pain-relevant gene signatures. CytoTRACE and Slingshot were used to assess relative transcriptional complexity and infer state-transition trajectories. CellChat analysis of pooled cells from all groups was performed to predict intercellular communication, and SCENIC was used to characterize subpopulation-associated regulon activity.
resultsA total of 66,310 cells were retained, including 7648 microglia that were resolved into eight transcriptionally distinct subpopulations. Among them, the Lars2
conclusionThis study identifies the Lars2
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