Fig. 7: Specific genetic pain-relief mechanism in spatially-constrained strategy.

a Visualization of common and differentially expressed genes among groups treated with 4:4 traditional conduits (TC), 4:4 traditional conduits + VP inhibition (TC + VP), 4:2 spatially confined conduits (CC), 4:2 spatially confined conduits  + VP (CC + VP), and untreated control group. b Number of differentially expressed genes in comparisons between CC vs. TC, and CC + VP vs. CC. [*P < 0.05, |log2 (fold change) | > 1]. c GO annotations analysis focusing on synaptic parts, development processes, cellular component organization, localization, and immune system processes. d GO enrichment analysis targeting T-helper 1 type immune responses, interleukin-10 production, regulation of neuroinflammatory responses, remyelination processes, and negative regulation of axon extension. e KEGG pathway enrichment analysis for cell adhesion molecules, NF-kappa B signaling pathway, axon guidance, and Hippo signaling pathway. f Volcano plot displaying all differentially expressed genes between CC and TC groups, with specific annotations for genes involved in anti-inflammatory, pro-inflammatory, mechanotransduction, remyelination, and pain activation pathways. g GSEA highlighting various processes of concern. These processes were compared between CC and TC, as well as between CC + VP and CC. All pairwise comparison groups exhibited P-values <0.05. h Heatmap of gene expression related to the Hippo signaling pathway across experimental groups. (n = 3). i Quantitative RT-PCR analysis of genes associated with mechanotransduction, remyelination, immune response, and pain resolution. (n = 3). Mean values are shown and error bars represent ± s.d., as analyzed by two-sided Student’s t-test in (i). Data are presented as means ± SD. *P < 0.05, **P < 0.01, ***P < 0.001.