Fig. 1

ApoE4 enhanced neuropathic pain sensitivity in mice. (A) Schematic of experimental design, SNI surgery, and von Frey filament test. (B) Mechanical thresholds of ApoE3-TR mice and ApoE4-TR mice before and after SNI. n = 10 mice per group. Cohen’s d for ApoE3-TR vs. ApoE4-TR post-SNI: 1.26 (D7), 1.46 (D14), 1.29 (D28). (C) Schematic diagram of DigiGait™ analysis. (D, E) Quantification of foot swing (D) and foot cycle (E) during DigiGait™ analysis of ApoE3-TR mice and ApoE4-TR mice before and 14 days after SNI. n = 6 mice per group. Cohen’s d = 2.71 for foot swing and 2.06 for foot cycle (ApoE3-TR SNI vs. ApoE4-TR SNI). (F) Schematic diagram of mechanical pain-evoked Ca²⁺ signals recording. CMOS, complementary metal oxide semiconductor. (G) Heatmap showing the GCaMP6f fluorescence changes in the superficial dorsal horn of the spinal cord in ApoE3-TR and ApoE4-TR mice following pain stimulation 14 days after SNI. n = 10 mice per group. (H) Peri-event plot of GCaMP6f ΔF/F after pain stimulation. (I) Quantification of the mean AUC value for ApoE3-TR and ApoE4-TR mice. n = 10 mice per group. (J) Representative images of the spinal dorsal horn labeled with anti-ApoE (red), anti-GFAP (green), and anti-Iba1 (gray) antibodies in ApoE3-TR and ApoE4-TR mice 14 days after SNI. Scale bar, 30 μm (left), 10 μm (right). All data are expressed as mean ± SEM. Statistical comparisons were conducted with two-way ANOVA followed by Bonferroni’s post hoc test (B); one-way ANOVA followed by Tukey’s post hoc test (D, E); and unpaired Student’s t-test (I). *P < 0.05, **P < 0.01, and ***P < 0.001