Disruption of the NaV1.7–CRMP2 interaction alleviates mechanical allodynia without affecting physiological pain. (A) CRMP2-binding intensity to NaV1.7-derived peptide #141 from contralateral (Contra) and ipsilateral (Ipsi) spinal cords of male rats taken two weeks following SNI (n = 4). (B) Time course for male and female rats following administration of Myr-TAT-SCR, or Myr-TAT-NaV1.7-CRS (20 µg in 5 µL, i.t.). (C) Area under the curve for paw withdrawal thresholds showing that Myr-TAT-NaV1.7-CRS reversed mechanical allodynia, n = 6 rats; (D) Cartoon and bar graph with scatter plot of paw withdrawal latency in the hot plate test (52 °C) (n = 10 mice). (E) Cartoon and bar graph with scatter plot of the tail flick (52 °C) test showing no effect of the Myr-TAT-NaV1.7-CRS (n = 10 mice). (F) Cartoon of the rotarod apparatus to assess motor coordination in rodents. Bar graph with scatter plot showing the latency to fall off a rotating rod was not different between the treatments. n = 7 rats; error bars indicate mean ± SEM; Mann–Whitney U test, Kruskal–Wallis, or two-way ANOVA (details are in Dataset S1), P values as indicated. The experiments were conducted by investigators blinded to treatments.