Extended Data Fig. 8: Biological pattern amplification in chronic pain spread.

a, Schematic of chronic pain spreading, quantified by the total number of chronic pain sites, alongside the investigated biological modalities: blood, brain, bone, and genetics. Biological patterns, represented by structure coefficients, associated with pain spread severity were derived from models distinguishing between levels of pain spread severity, ranging from low (one chronic pain site versus pain-free) to high (four or more chronic pain sites versus pain-free). b, Structure coefficients from models are shown for each level of pain spread, ordered by severity and segmented by subcategory. Additionally, coefficients for a generalized chronic pain model, encompassing any number of pain sites, are also shown. c, Cortical surface renderings visualize resting functional connectivity, thresholded to highlight the top 25% of structure coefficients, which represent the sum of dynamic conditional correlation across brain parcels. Arrows interlinking the cortical renderings depict the association (two-sided Pearson correlation, all P < 0.001 bonferonni corrected) between the complete unthresholded vectors of structure coefficients (parcel to parcel connectivity) for adjacent levels of pain spread. d, Skeletal body maps show bone segments colored based on structure coefficients for each assessed bone system, using DXA-derived bone density, mineral content, and area estimates. For each spreading level, averages of these three estimates for each bone system (e.g., head, spine, leg) are depicted on the maps. e, Heritability estimates derived from polygenic risk scores (PRS) are shown. These heritability estimates are significant according to a two-sided, FDR-corrected Wald Test (all P < 0.001). The top 5% of FDR-corrected gene ontology pathways for each PRS are tallied and organized by biological process. The corresponding bars are shaded based on the average explained variance (R²) across pathways within each biological process.