Compound 9 (DA-0218) is effective against paclitaxel-induced mechanical allodynia in neuropathic pain mouse model when introduced intrathecally but not intraperitoneally. (A to C) Intrathecal DA-0218 produced statistically significant antiallodynia effects in paclitaxel-induced neuropathic pain in a mixture of male and female mice (A, two-way repeated measures ANOVA time × treatment interaction F[12, 140] = 8.519; P < 0.0001; post hoc pairwise P values are Bonferroni-corrected for three tests), male mice (B, two-way repeated measures ANOVA time × treatment interaction F[8, 40] = 8.998; P < 0.0001; post hoc pairwise P values are Bonferroni-corrected for two tests) and female mice (C, two-way repeated measures ANOVA time × treatment interaction F[12, 88] = 3.575, P < 0.001; post hoc pairwiseP values are Bonferroni-corrected for three tests). Shown experimental data include 5 to 13 mice per group. (D) Repeated intrathecal injections of DA-0218 induced acute tolerance (repeated measures one-way ANOVA F[1.968, 13.78] = 46.56; P < 0.0001; post hoc pairwise P values are Bonferroni-adjusted for four tests). Experimental sample size n = 8 mice. (E) Intrathecal PE-05089771 did not produce antiallodynia effects in paclitaxel-induced neuropathic pain model (repeated measures two-way ANOVA time × treatment interaction F[4, 48] = 0.036; P = 0.991; post hoc pairwise P values are Bonferroni-corrected, n = 6, eight mice per group). (F) Intraperitoneal DA-0218 did not produce any antiallodynia effects in paclitaxel-induced neuropathic pain model (repeated measures two-way ANOVA time × treatment interaction F[8, 48] = 0.244; P > 0.999; post hoc pairwise P values are Bonferroni-corrected; n = 5 mice per group).