The Mediating Role of White Matter Integrity and Grey Matter Volume in the Relationship between Pain and Neurocognitive Function

Abstract

Introduction: Pain is a pervasive, disruptive, and costly public health concern. In addition to physical disability and impairment, pain is associated with cognitive dysfunction across all age groups. Numerous neuroimaging studies have shown alterations in the grey and white matter of patients with chronic pain, leading researchers to hypothesize that these changes may in part contribute to pain-related cognitive deficits. Accordingly, the purpose of the present study was to evaluate the possible mediating role of brain structural features (grey matter volumes and white matter integrity) in the relationship between pain and neurocognitive functioning. Methods: Participants were 200 self-identified African American and White adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Participants underwent structural cranial magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). Grey matter volume was estimated from the structural MRI scans, while white matter integrity was defined using fractional anisotropy values from DTI scans. Pain interference was measured with the bodily pain subscale from the SF-12. Parallel mediation analyses examined if grey matter volume in the prefrontal cortex (middle, dorsolateral, and orbitofrontal) and anterior insula mediated the relationship between pain interference and cognitive function. Parallel mediation analyses were also used to examine if white matter integrity in the anterior limb of the integral capsule, external capsule, and cingulum bundle mediated the relationship between pain interference and cognitive function. Simple mediation analyses examined if anterior cingulate cortex volume mediated the relationship between pain interference and cognitive function. All models were adjusted for age, sex, race, drug use, socioeconomic status (SES), and depression. Measures of cognition included Trails A, Tails B, Digit Span Forward, Digit Span Backward, and the Stroop task. Results: Higher pain interference was related to worse performance on Trails B and on the Stroop in some models. Pain interference was not significantly associated with grey matter volumes in any of the regions of interest. Increased pain interference was associated with reduced white matter integrity in the anterior limb of the internal capsule and the external capsule. However, these tracts did not mediate the relationship between pain interference and cognitive function. Conclusions: Results indicated that pain interference was associated with performance on some tests of executive function and processing speed. Additionally, increased pain interference was associated with reductions in white matter tracts that support important executive functions, although these alterations did not mediate the relationship between pain interference and tests of executive function. Further research is needed to determine if pain is a contributor to or a consequence of these white matter changes and to determine the underlying biological mechanisms driving these alterations. However, these results support pain treatment as a way to promote neurobiological health and cognitive function.