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. 2014 Jan 21;111(6):2325–2330. doi: 10.1073/pnas.1308889111

Fig. 2.

Fig. 2.

XIB4035 treats line-D mice with advanced SFN symptoms. (A) Hot-plate (54 °C) test shows XIB4035 improves the SFN symptoms of line-D mice when treatment is initiated after severe symptoms are apparent (P28). Mutant mice showed significant improvement in thermal nociception after 1 wk of treatment (P35), and this was maintained as long as the treatment continued [red line indicates treatment duration; one-way ANOVA Newman–Keuls post hoc test, n ≥ 7; line-D +vehicle vs. line-D +XIB4035; n.s., not statistically significant; **P < 0.01, ***P < 0.001; WT +vehicle vs. line-D +vehicle, P < 0.001, WT +vehicle vs. line-D +XIB4035, P < 0.001 (P28, P35, P42), P < 0.01 (P49), P > 0.05 (P56); error bars indicate SEM]. (B) Chronic XIB4035 treatment is necessary to maintain gains. If mice were treated beginning at P28 (as in A), but treatment was interrupted at P35, neuropathic symptoms returned [red line indicates treatment duration; one-way ANOVA Newman–Keuls post hoc test, n ≥ 7; line-D +vehicle vs. line-D +XIB4035; n.s., not statistically significant; *P < 0.05, ***P < 0.001; WT +vehicle vs. line-D +vehicle, P < 0.001; WT +vehicle vs. line-D +XIB4035, P < 0.001 (P28, P35, P42, and P49), P < 0.01 (P56); error bars indicate SEM]. (C) If XIB4035 treatment is initiated at P28, the sensory recovery at P35 is not accompanied by recovery of IENF density. Representative images of PGP9.5-positive IENF staining at P35 in line-D hindpaw skin. (Scale bar: 100 μm.) (D) XIB4035 treatment initiated at P28 results in improved IB4 staining in the dorsal spinal cord. (Left) Representative images of spinal cord sections from wild-type mice treated with vehicle from P28 to P35 show the normal appearance of TrpV1+ (red) and IB4+ (green) nerve terminals. (Center) Images of line-D mice treated with vehicle show complete absence of IB4 staining. (Right) Images from line-D mice treated with XIB4035-containing cream show clear presence of IB4+ fibers. No obvious difference in TrpV1 labeling was observed between wild-type and mutant animals regardless of treatment. (Scale bar: 50 μm.)