Figure 3.

Sex differential aspects of the pain-associated transcriptome. (A) The top 25 pain-associated genes (Supplementary Table 3A and C) increased in pain (with a median fold change of 2-fold or higher) for each sex show a remarkably sex-differential signal, with only HAMP showing 2-fold or greater change in the median in both sexes among the top 25. Log2 fold changes in the median between pain and no-pain subcohorts are shown for males and females as a scatter plot, with male pain-associated genes shown in blue (right cluster) and female pain-associated genes shown in pink (left cluster). LY96 is present in both male and female lists. (B) Pain-associated ligands in each sex signal to hDRG-expressed receptors that are enriched in sensory neuronal subpopulations,¹¹ but have little overlap across sexes. Based on our interactome analysis, we show such ligand–receptor pairs, alongside receptor expression in human DRG neuronal subtypes¹¹ as a heatmap. Overlap with relevant signalling pathways are also shown. Male signalling is enriched in TNF-alpha pathway, while female signalling is enriched in interferon signalling. Although ICAM3 (in males) and TGFB2 or NOV (in females) are not in the pain-associated gene lists, they are increased in pain for the corresponding sex at the median or upper quartile levels and are thus shown here.