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Juvenile fibromyalgia (JFM) is a chronic widespread pain condition that primarily affects adolescent girls. Previous studies have found increased sensitivity to noxious pressure in adolescents with JFM. However, the underlying changes in brain systems remain unclear. The aim of this study was to characterize pain-evoked brain responses and identify brain mediators of pain hypersensitivity in adolescent girls with JFM. Thirty-three adolescent girls with JFM and 33 healthy adolescent girls underwent functional magnetic resonance imaging scans involving noxious pressure applied to the left thumbnail at an intensity of 2.5 or 4 kg/cm² and rated pain intensity and unpleasantness on a computerized Visual Analogue Scale. We conducted standard general linear model analyses and exploratory whole-brain mediation analyses. The JFM group reported significantly greater pain intensity and unpleasantness than the control group in response to noxious pressure stimuli at both intensities (P < 0.05). The JFM group showed augmented right primary somatosensory cortex (S1) activation to 4 kg/cm² (Z > 3.1, cluster-corrected P < 0.05), and the peak S1 activation magnitudes significantly correlated with the scores on the Widespread Pain Index (r = 0.35, P = 0.048) with higher activation associated with more widespread pain. We also found that greater primary sensorimotor cortex activation in response to 4 kg/cm² mediated the between-group differences in pain intensity ratings (P < 0.001). In conclusion, we found heightened sensitivity to noxious pressure stimuli and augmented pain-evoked sensorimotor cortex responses in adolescent girls with JFM, which could reflect central sensitization or amplified nociceptive input. [ABSTRACT FROM AUTHOR]