Diffusion tensor imaging of white matter microstructure in chronic pain: a tract-based spatial statistics study and a systematic review

The pathophysiology of many chronic pain disorders is far from evident. MR imaging studies provided initial data indicating chronic pain might lead to changes in brain structure and function. These changes may contribute to cognitive and emotional impairment and maybe even to the chronification of pain. However, the evidence for pain-related changes in gray and white matter is inconclusive so far. Hence we investigated potential changes of white matter microstructure in 34 adults with chronic noncancer pain (> 1 year) and 34 sex- and age-matched healthy individuals using diffusion tensor imaging (DTI). Whole-brain tract-based spatial statistics (TBSS) analyses of fractional anisotropy, mode of diffusivity, mean diffusivity, axial diffusivity, and radial diffusivity did not show significant differences after correction for multiple comparisons. The volumes of subdivisons of the corpus callosum were not significantly different either. We also performed a systematic review of the existing literature on white matter microstructure in patients with chronic pain following PRISMA guidelines. We identified 53 eligible studies on DTI in chronic pain. These studies demonstrated conflicting results regarding the direction and location of white matter changes across all diagnoses and within major diagnostic subcategories. We propose that two factors primarily contribute to this low reproducibility, small sample size and the use of potentially unreliable DTI parameters derived from the single-tensor model.