(A–I) Nociceptive thresholds to mechanical (A), cold (D), and heat (G) stimulation of the hindpaws of adult male Sprague-Dawley rats treated with vehicle (EtOH/Kolliphor EL/PBS, 1:1:6, i.p.) or PTX (11.7 mg/kg, i.p.) on days 0, 2, and 4. Data represent the mean change from baseline ± SEM. Individual rat timecourse plots showing changes in mechanical (B), cold (E), or heat (H) sensitivity following vehicle or PTX treatment. Bold lines represent group means. Area under the timecourse curves (AUC) of mechanical (C), cold (F), or heat (I) thresholds from vehicle- or PTX-treated rats. Bars represent the mean ± SEM and small circles are individual rat AUC values. ****p<0.0001, **p<0.01, *p<0.05 vs. Veh by two-way mixed effect ANOVA with Sidak’s post-hoc test (A, D, G) or two-tailed Student’s t-test (C, F, I), n = 14–15 rats/group. (J) Confocal images of IENFs in rat hindpaw biopsies. IENFs immunolabeled with PGP9.5 (arrowheads) project from subepidermal fascicles across the epidermal-dermal junction. Scale bar, 100 μm. (K) Confocal images of ATF3 expression (arrowheads) in nuclei of DRG neurons (also labeled with NeuN) acquired on day 7. Scale bar, 100 μm. (L and M) Quantification of IENF densities from paw biopsies collected on day 7 (L) and day 16 (M) of the experimental paradigm. Bars represent the mean ± SEM calculated from individual rat IENF densities from each group (circles), n = 7 rats/group. (N) Quantification of ATF3 expression. Bars represents mean ± SEM from each group, n = 3 rats/group. ****p<0.0001, ***p<0.001 vs. Veh by two-tailed Student’s t-test (L–N).