Effect of preterm birth, sex, and time on pressure pain threshold during conditioned pain modulation (CPM). (a) Change in mechanical pressure pain threshold over the right fibula head (PPT, raw data, kPa) in term control (TC) and extremely preterm (EP)-born young adults during (15 s) and after (50 and 90 s) a conditioning stimulus (0–30 s). Females unable to tolerate immersion until the parallel PPT measurement (<15 s) had no significant change in PPT with time. Additional groups with <15 s immersion were too small for analysis (five EP males, four TC females, and two TC males). Data points=mean [95% confidence interval (CI)]. (b) and (c) Change in log-normalised PPT (ln kPa) with time in (b) males and (c) females. For EP and TC participants tolerating at least 20 s conditioning, PPT is significantly increased above baseline at 15 and 50 s. In EP females with <15 s immersion, a minor increase in threshold is seen only at 15 s. Data points=mean (95% CI). ###P<0.001, #P<0.05, ***P<0.001, **P<0.01, *P<0.05, §P<0.05; two-way repeated measures analysis of variance with Bonferroni post hoc comparisons of within-group change compared with baseline.