R-47 prevents CIPN in mice. A) Chronic administration of R-47 at a dose of 10 mg/kg p.o. completely prevents the development of mechanical hypersensitivity. **** P < 0.0001 Veh-Veh vs Veh-Pac; #### P < 0.0001 R-47-Pac vs Veh-Pac; BL, baseline; Veh, Vehicle; Pac, Paclitaxel. n=8 per group; Data expressed as mean ± SEM. B) Mice injected with paclitaxel at a dose of 8 mg/kg i.p. for one cycle demonstrate a significant reduction of IENFs at 35 days post-paclitaxel injection. However, pre- and co-administration of R-47 at a dose of 10 mg/kg p.o. to paclitaxel-treated mice completely prevents the reduction of IENFs; *P < 0.0001 D.W.-paclitaxel vs D.W.-vehicle; #P < 0.0001 R-47-paclitaxel vs D.W.-paclitaxel. C) Immunostained sections of hind paw epidermis represent the reduction of IENF density by paclitaxel and protection by R-47. Bar represents 20 microns in all images. Images were captured under 63x magnification. IENFs, intra-epidermal nerve fibers; D.W., distilled water. Asterisks denote IENFs. n = 6 per group; data expressed as mean ± SEM.