Can Pain Neuroscience Education Combined with Cognition-Targeted Exercise Therapy Change White Matter Structure in People with Chronic Spinal Pain? A Randomized Controlled Trial.

White matter (WM) structural changes have been found in patients with chronic spinal pain (CSP). In these patients, pain neuroscience education followed by cognition-targeted exercise therapy (i.e., the Modern Pain Neuroscience Approach (MPNA)) was shown to be more effective than biomedically-focused education followed by symptom-contingent exercise therapy for improving clinical outcomes. The present study examined whether an MPNA, compared to biomedically-focused treatment, can change WM structure in regions of interest and whether potential WM structural changes are associated with clinical improvements in patients with CSP. : Patients with CSP were randomized into an experimental (MPNA) or control (biomedically-focused) treatment group. Diffusion-weighted Magnetic Resonance Images were acquired pre-treatment, post-treatment, and at 1-year follow-up. WM structure was assessed using diffusion tensor imaging in 8 WM regions of interest, and linear mixed models assessed differences between groups in response to treatment. : No significant treatment x time interaction effects were found; however, significant main effects of time were found in 7 WM tracts. Significant main effects of time revealed increased fractional anisotropy (FA), decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in the cingulum hippocampus, and decreased RD and MD in the superior cerebellar peduncle at 1-year follow-up compared to baseline. In contrast, decreased FA and/or increased MD, AD, or RD values were found in other WM tracts (e.g., anterior corona radiata) from pre-treatment to 1-year follow-up. Greater reduction in kinesiophobia was moderately correlated with a smaller decrease in RD in the superior cerebellar peduncle at 1-year follow-up compared to baseline. No other significant associations were found between WM structural changes and clinical improvements. : In conclusion, in patients with CSP, regional WM structure changed over time irrespective of prescribed treatment (timespan of 12 months). Further research, including Neurite Orientation Dispersion and Density Imaging and a healthy control group, allowing for a more specific examination of WM microstructural changes in response to multimodal treatment in patients with CSP, is warranted.