Fig. 1: Contextual pain hypersensitivity in response to pain conditioning in male, but not female, mice.

a Schematic for the contextual pain hypersensitivity mouse model. b, c Example raster plots and statistic data for writhing and constriction reponses of saline- and AA-injected male and female mice (n = 5; Writhing, F_3,16 = 13.51, p = 0.0001; Constriction, F_3,16 = 58.05, p < 0.0001). d, e Paw withdrawal threshold (PWT) and latency (PWL) of the male^DC, female^DC, male^SC, and female^SC mice (PWT: n = 7 for male^DC, p = 0.4812; n = 6 for female^DC, p = 0.5208; PWL: n = 5 per group, p = 0.6061 for male^DC, p = 0.7439 for female^DC; PWT: n = 10 for male^SC, p < 0.0001; n = 7 for female^SC, p = 0.8053; PWL: n = 9 per group, p = 0.0045 for male^SC, p = 0.7832 for female^SC). f, g PWT and PWL for 7 days after AA injection in male and female mice (PWT: n = 6 per group, F_1,10 = 20.48, p = 0.0011; PWL: n = 5 for male^DC, n = 9 for male^SC, F_1,12 = 5.137, p = 0.0427; PWT: n = 5 for female^DC, n = 4 for female^SC, F_1,7 = 0.4099, p = 0.5424; PWL: n = 5 for female^DC, n = 9 for female^SC, F_1,12 = 4.676, p = 0.0515). h Schematic for the auditory-cue-induced contextual pain hypersensitivity paradigm. i PWT and PWL of the male^DC and male^SC mice (n = 5 per group; PWT, F_1,8 = 3.169, p = 0.0288; PWL, F_1,8 = 7.233, p = 0.0275). j As indicated in panel i, but for female mice (n = 5 per group; PWT, F_1,8 = 0.1501, p = 0.7086; PWL: F_1,8 = 0.2094, p = 0.6594). Significance was assessed by one-way ANOVA with post hoc Bonferroni’s test between groups in c, two-tailed paired Student’s t-test (d, e) and two-way repeated-measures ANOVA with post hoc comparison between groups (f–j). The data are presented as the mean ± SEMs. * P < 0.05, ** P < 0.01, *** P < 0.001; n.s. not significant. See also Supplementary Table 1. Source data are provided as a Source Data file.