Pain differences in neurite orientation dispersion and density imaging measures among community-dwelling older adults

Neurite orientation dispersion and density imaging (NODDI) is a technique providing more detailed information on the microstructural bases of white matter. Given the previously reported white matter contributions to chronic pain, the present study aims to investigate pain-specific differences in NODDI measures across white matter tracts in a sample of community-dwelling older adults with (n = 29) and without (n = 18) chronic musculoskeletal pain. We further aimed to investigate associations between NODDI measures and clinical and experimental pain measures. As part of the Nepal study, a subset of older adults (>60 years old), underwent multiple laboratory sessions providing self-reported and experimental pain measures and a diffusion weighted neuroimaging sequence. Older adults with chronic musculoskeletal pain had a lower neurite density with less geometric complexity across a number of white matter tracts compared to older pain-free controls (corrected p's < 0.05). Lower neurite density was associated with greater self-reported pain intensity and anatomical pain sites, as well as greater experimental pain sensitivity (p's < 0.05). There were also significant pain-by-sex differences in neurite density and geometric complexity across multiple white matter tracts mainly around the hippocampus (corrected p's < 0.05). Finally, there were no pain differences with respect to extra-cellular water diffusion (corrected p's > 0.05). Our study demonstrates less geometric complexity in neurite density and architecture in chronic musculoskeletal pain, partly in a sex-dependent manner. An increased understanding of neurobiological mechanisms such as those measured by NODDI may contribute to the potential targeting of interventions in our older population suffering from chronic pain.