Figure 2. P7C3-A20 abrogates neuropathic pain and protects peripheral sensory neurons from PTX-induced damage.

(A–C) Nociceptive thresholds to mechanical (A), cold (B), and heat (C) stimulation of the hindpaws of rats treated daily with vehicle (DMSO/Kolliphor EL/PBS, 1:4:10, i.p.) or P7C3-A20 (10 mg/kg/day, i.p.), in addition to vehicle or PTX treatment on days 0, 2, and 4 as before (Figure 1). Data represent the mean change from baseline ± SEM. (D–F) Treatment group AUCs of mechanical (D), cold (E), or heat (F) thresholds. Bars represent the mean AUC ±SEM and small circles are individual rat AUC values. ****p<0.0001, **p<0.01, *p<0.05 by one-way ANOVA with Dunnett’s post-hoc test, n = 5–8 rats/group. (G and H) Confocal images of IENFs in rat hindpaw biopsies (G, scale bar: 100 μm) and ATF3 expression in lumbar DRG (H, scale bar: 50 μm.) (I) IENF densities from hindpaw biopsies collected on days 7 and 16 of the experimental paradigm. Bars represent the mean ±SEM calculated from individual rat IENF densities from each group (circles), n = 5–8 rats/group. (J) ATF3 expression in lumbar DRG perikarya collected on day 7. Bars represents mean ± SEM from each group, n = 3 rats/group. ****p<0.0001, **p<0.01 vs. Veh/PTX by one-way ANOVA with Tukey’s post-hoc test (I and J).

Figure 2—figure supplement 1. Effects of P7C3-A20 on PTX-induced weight loss and leukopenia.

(A) Adult male Sprague-Dawley rats received P7C3-A20 (10 mg/kg/day, i.p.) beginning 2 days prior to the first injection of PTX (11.7 mg/kg, i.p., q.a.d.) or vehicle. Blood samples were collected and responses to noxious mechanical, cold, and heat stimulation were measured before, during, and after treatment as indicated. (B and C) P7C3-A20 did not affect PTX-induced weight loss (B) or leukopenia (C). Data are expressed as mean ±SEM, n = 6–8 rats/group (weight) or 4 rats/group (leukocyte counts). #p<0.0001, $p<0.001, **p<0.01, *p<0.05 vs. vehicle-treated controls by two-way mixed effect ANOVA with Sidak’s post-hoc test.