Extended Data Figure 6 |. Paw withdrawal thresholds and in situ intensity measurements.

a, Paw withdrawal thresholds (PWT) before (blue bar) and after (red bar) spared nerve injury (SNI), as well as after SNI + treatment (purple bar). For easier visualization of individual data points, data was also plotted without the pre-SNI baseline. Data are the same as in Figure 4b and Extended Data Figure 4a, but without the normalization to the individual post-SNI baselines and are expressed as mean ± SEM; mice per group: saline (n = 10); cyclodextrin (n = 10); kolliphor (n = 5); PB28 30 mg/kg (n = 10); PD-144418 10 mg/kg (n = 5) and 30 mg/kg (n = 5); Z4446724338 10 mg/kg (n = 10) and 20 mg/kg (n = 5); Z1665845742 10 mg/kg (n = 5) and 20 mg/kg (n = 5); Z4857158944 10 mg/kg (n = 5) and 20 mg/kg (n = 5); unpaired two-tailed Student’s t-test. b, PWTs 1 hour, 24 hours, and 48 hours after saline or drug treatment. Data are the same as in Figure 4c, but without the normalization to the individual post-SNI baselines, and are expressed as mean ± SEM. Significance levels determined using Dunnett’s multiple comparisons Post-hoc test reflect the difference between Z4446724338 and saline for simplicity (two-way ANOVA; time × treatment interaction: F(8, 80) = 2.4, p = 0.02; time: F(2, 74) = 5.2, p = 0.009; treatment: F(4, 40) = 3.3, p = 0.02; four treatment groups (n = 10) except PD-144418 (n = 5); ns = not significant. c, Response of SNI mice to a von Frey filament after repeated injections of Z4446724338 10 mg/kg (n = 5). Mechanical thresholds were assessed 1 hour and 24 hours after four separate injections. Data shown are paw withdrawal thresholds in grams, expressed as mean ± SEM. d, Response of SNI mice to a von Frey filament after repeated injections of Z4857158944 10 mg/kg (n = 5). Mechanical thresholds were assessed 1 hour and 24 hours after four separate injections. Data shown are paw withdrawal thresholds in grams, expressed as mean ± SEM.