Brain mechanisms supporting nonpainful multisensory hypersensitivities associated with core disease symptoms in youth with chronic primary pain

Abstract Juvenile fibromyalgia (JFM) is a chronic primary pain condition mostly affecting adolescent females during a critical period of brain development. Clinical reports have described nonpainful sensory symptoms in JFM. For the first time, we investigated whether girls with JFM showed augmented sensory hypersensitivity in daily life and in an experimental setting and studied the neurophysiological substrates using functional magnetic resonance imaging (fMRI). We included 90 female adolescents (46 girls with JFM and 44 healthy girls) that completed measures of multisensory hypersensitivity in daily life, auditory tasks assessing potential auditory and attentional impairments, and an fMRI multisensory task involving processing of concurrent visual, auditory, and tactile-motor stimulation. We compared between-group differences in task-evoked brain activation and examined associations between brain activation and core symptoms. Juvenile fibromyalgia patients reported higher multisensory hypersensitivity in daily life and augmented unpleasantness during the multisensory task ( P < 0.0001). We found no significant between-group differences neither in the tasks assessing auditory impairments ( P > 0.15) nor in brain activation during multisensory stimulation ( P FWE-cluster > 0.05). However, in JFM patients, we found strong correlations between task-evoked activation in sensory integration and prefrontal cortex regions ( P FWE-cluster > 0.05, P voxel < 0.001) and disease symptoms. Our results suggest that increased sensory integration and prefrontal responses may serve as key neurobiological correlates of disease severity and sensory hypersensitivity in JFM.