White matter microstructural associations with pain experiences in a large community sample of youth

Pain experiences in adolescence are increasing and represent a major public health concern. However, little is known about the neurobiological phenotype of pain experiences in adolescents, particularly outside of a clinical setting. A better neurobiological understanding of pain experiences in community youth may shed light on potential vulnerabilities present before clinical diagnoses of chronic pain. This study utilized an exploratory region-of-interest approach, in a large community sample (n = 7332) of youth (ages 11-12), to examine the association between white matter microstructure, fractional anisotropy (FA) and mean diffusivity (MD), and pain experiences. Bayesian multilevel modeling was used to explore group differences (between those reporting past-month pain and those who did not), and continuous associations between pain experiences (average pain intensity, worst pain intensity, and pain-related limitations) and FA and MD. Sex differences in these effects were also explored. Analyses revealed widespread associations between pain-related limitations and lower FA and greater MD in male but not female youth. Furthermore, average pain intensity was associated with greater superior corticostriate and superior longitudinal fasciculus MD in all youth, and worst pain intensity was associated with lower inferior fronto-occipital fasciculus FA in male youth. There were no group differences in FA or MD between those with or without past-month pain. These findings suggest that white matter microstructural alterations in youth may be more related to the severity of the pain experience than to the presence or absence of pain itself, with male youth showing stronger neurobiological associations with pain-related outcomes.