IL-4 induces opioid peptide release from M1 macrophages from injured nerves. Extracellular levels of ENK, END, and DYN secreted from F4/80+ macrophages isolated by IMS from injured nerves on day 14 after CCI and stimulated ex vivo (5 min) with IL-4 (10–200 ng/ml) or vehicle (PBS). Opioids were measured by EIA. The data in vehicle groups are the same in all graphs, to reduce animal numbers (see also Materials and Methods). ENK (F(4,35) = 10.82, p < 0.0001), END (F(4,35) = 9.781, p < 0.0001; one-way ANOVA), DYN (Kruskal–Wallis statistic = 16.87, p = 0.0021); *p < 0.05, **p < 0.01, ***p < 0.001 versus vehicle; one-way ANOVA and Bonferroni's test (ENK, END) or Kruskal–Wallis one-way ANOVA and Dunn's test (DYN). Data are presented as individual data points and mean ± SEM N = 8 samples per group.