SCD iSNs show increased sensitivity to capsaicin in the presence of spermine. (A) Schematic of arginine and polyamine metabolism relevant for specific biochemicals related to pain and inflammatory state in SCD. (B) Fold-change expression of biochemicals involved in these pathways indicate upregulation of polyamines, including spermine and its metabolites, in both SS BL and SS IP plasma compared with in HCs (Welch t test; dark red and dark green boxes, P < .05; light red and light green, P > .05 but P < .10). (C) Box plots of selected targets from panel B showing quartiles and medians of distribution for metabolite scaled intensity. (D) Significantly increased sensitivity of HC iSNs and trend for increased sensitivity of SCD iSNs (P = .0949) to 10 μM capsaicin after a 30-minute 100 μM-spermine treatment (2-way ANOVA, ∗ P < .05, ∗∗P < .005). (E) Interestingly, significant increase SCD iSN response to previous subthreshold (1 μM) capsaicin compared to HC iSNs was induced by treatment with 100 nM, 100 μM, and 500 μM spermine concentrations (2-way ANOVA, ∗∗∗∗P < .0001).