Structural network differences in chronic muskuloskeletal pain: Beyond fractional anisotropy

Abstract

Chronic musculoskeletal pain is a condition that influences central nervous system structure. In this study, we combined novel structural neuroimaging techniques, using well-validated software packages including FSL, Mrtrix3, and DSI Studio, to characterize brain grey (GM) and white matter (WM) differences in chronic musculoskeletal pain participants (n = 74), compared to age-matched pain-free controls (n = 31). In participants with chronic pain, we identified significantly higher volume in subcortical GM structures using voxel-based morphometry (FSLVBM). These differences were most prominent in the caudate, amygdala, and the hippocampus. At the same time, volume was lower in the dorsolateral prefrontal cortex, as well as the primary motor and sensory regions in patients with chronic pain. To delineate WM microstructural differences of neuronal (e.g., activity-dependent myelin remodeling) and non-neuronal (e.g., neuroinflammation) origins, we utilized Mrtrix3 software pipelines to investigate WM fiber complexity, density, and cross-section. Whole-brain analyses revealed lower WM fiber complexity within the corpus callosum and the anterior limb of the left internal capsule. Whole brain and region of interest analyses revealed fiber complexity differences within the salience and the sensorimotor networks. In contrast, we detected non-neuronal white matter density differences within the dorsal attention network: density was lower in the inferior fronto-occipital fasciculus and the splenium of the corpus callosum in chronic musculoskeletal pain. Consistent with the involvement of the dorsal attention network, WM tractography analysis, conducted with DSI Studio and Network Based Statistics, revealed higher connectivity from the superior parietal lobule to the hippocampus in patients with chronic pain. No differences were detected in measures of fiber cross-section, suggesting the absence of neuronal degeneration in chronic pain. The combination of multiple neuroimaging techniques in this study offers a unique window into the structural differences within the chronic pain brain and provides the first evidence of microstructural variations in fiber complexity and density.

Keywords: Chronic pain; Diffusion magnetic resonance imaging; Diffusion tractography; Microstructure; VBM.