Extended Data Fig. 1: High volume CFA injection into the hindlimb footpad induces persistent mechanical allodynia.

a, Representative photograph of a mouse injected with high volume of CFA in the left hind paw (circled in yellow), showing visible fullness and swelling compared to the contralateral hindlimb footpad at day 20 post-injection. The inset highlights the difference between the CFA-injected (left) and the contralateral hindlimb footpad (right). Data are represented as mean ± s.e.m. b, Normalized mechanical withdrawal thresholds for high (n = 22) (red) and low (green) (n = 5) CFA volume animals over the experimental timeline. High CFA animals display a persistent reduction in withdrawal thresholds as compared to the low volume CFA animals. Low CFA animals display a transient mechanical hypersensitivity with thresholds returning to baseline by day 7 post-CFA injection compared to the contralateral limb (two-way ANOVA, P > 0.322 after day 7). c, Comparison of multiple mood-related behavioral responses (top: FST, TST; bottom: EPM, light/dark test, and OFT) between SNI (n = 20) and high-volume CFA (n = 22) mice. CFA mice display similar behavior to SNI mice across all mood-related tests (Kruskal–Wallis followed by Dunn’s multiple comparison: P > 0.10). Data are represented as mean ± s.e.m. **P < 0.01, ns = nonsignificant. Detailed statistics are reported in Supplementary Table 1h.