Fig. 5.
Compound 9 (DA-0218) inhibits transient sodium currents in isolated naive and paclitaxel pretreated mouse (A to D) and human (E and F) dorsal root ganglion neurons with small sizes (less than 25 μm and less than 55 μm in mouse and human, respectively). (A) Traces of sodium currents in mouse dorsal root ganglion neurons. (B) Time course of sodium currents in mouse dorsal root ganglion neurons with and without paclitaxel treatment (1 μM, 16 to 24 h). Statistically significant effect of 10 μM DA-0218 on sodium current was observed in naive (two-way repeated measures ANOVA time × treatment interaction F[41, 369] = 4.072; P < 0.0001) and paclitaxel-treated dorsal root ganglion neurons (F[41, 492] = 7.147, P < 0.0001). (C) Paclitaxel treatment (1 µM, 24 h) increased transient sodium currents in cultured mouse dorsal root ganglion neurons (t[43] = 1.416; P = 0.1640 with outliers [solid circles] and t[40] = 4.023; P < 0.001 without outliers). Sample size is n = 16 to 29 neurons per group from three to six mice. (D) DA-0218 produced more potent inhibition in paclitaxel pretreated mouse dorsal root ganglion neurons (t[11] = 2.292; P = 0.043 with outlier and t[10] = 3.148, P = 0.010 without outlier). Sample size is n = 7 neurons/group from three mice. (E) Traces of sodium currents in human dorsal root ganglion neurons. (F) Time course of sodium currents in human dorsal root ganglion neurons (two-way repeated measures ANOVA time × treatment interaction F[42, 294] = 3.362; P < 0.0001; treatment main effect). Sample size is n = 4 to 5 neurons per group from two donors. Mean relative current at the last measurement was 73% of the baseline in human dorsal root ganglion neurons and 72% (43% in paclitaxel-treated) in mouse dorsal root ganglion after DA-0218 treatment.

Compound 9 (DA-0218) inhibits transient sodium currents in isolated naive and paclitaxel pretreated mouse (A to D) and human (E and F) dorsal root ganglion neurons with small sizes (less than 25 μm and less than 55 μm in mouse and human, respectively). (A) Traces of sodium currents in mouse dorsal root ganglion neurons. (B) Time course of sodium currents in mouse dorsal root ganglion neurons with and without paclitaxel treatment (1 μM, 16 to 24 h). Statistically significant effect of 10 μM DA-0218 on sodium current was observed in naive (two-way repeated measures ANOVA time × treatment interaction F[41, 369] = 4.072; P < 0.0001) and paclitaxel-treated dorsal root ganglion neurons (F[41, 492] = 7.147, P < 0.0001). (C) Paclitaxel treatment (1 µM, 24 h) increased transient sodium currents in cultured mouse dorsal root ganglion neurons (t[43] = 1.416; P = 0.1640 with outliers [solid circles] and t[40] = 4.023; P < 0.001 without outliers). Sample size is n = 16 to 29 neurons per group from three to six mice. (D) DA-0218 produced more potent inhibition in paclitaxel pretreated mouse dorsal root ganglion neurons (t[11] = 2.292; P = 0.043 with outlier and t[10] = 3.148, P = 0.010 without outlier). Sample size is n = 7 neurons/group from three mice. (E) Traces of sodium currents in human dorsal root ganglion neurons. (F) Time course of sodium currents in human dorsal root ganglion neurons (two-way repeated measures ANOVA time × treatment interaction F[42, 294] = 3.362; P < 0.0001; treatment main effect). Sample size is n = 4 to 5 neurons per group from two donors. Mean relative current at the last measurement was 73% of the baseline in human dorsal root ganglion neurons and 72% (43% in paclitaxel-treated) in mouse dorsal root ganglion after DA-0218 treatment.

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