Increased white matter diffusivity associated with phantom limb pain

Background: We utilized diffusion tensor imaging (DTI) to evaluate the cerebral white matter changes that are associated with phantom limb pain in patients with unilateral arm amputation. It was anticipated that this would complement previous research in which we had shown that changes in cerebral blood volume were associated with the cerebral pain network. Methods: Ten patients with phantom limb pain due to unilateral arm amputation and sixteen healthy age-matched controls were enrolled. The intensity of phantom limb pain was measured by the visual analogue scale (VAS) and depressive mood was assessed by the Hamilton depression rating scale. Diffusion tensor-derived parameters, including fractional anisotropy, mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD), were computed from the DTI. Results: Compared with controls, the cases had alterations in the cerebral white matter as a consequence of phantom limb pain, manifesting a higher AD of white matter in both hemispheres symmetrically after adjusting for individual depressive moods. In addition, there were associations between the RD of white matter and VAS scores primarily in the hemispheres related to the missing hand and in the corpus callosum. Conclusions: The phantom limb pain after unilateral arm amputation induced plasticity in the white matter. We conclude that loss of white matter integrity, particularly in the hemisphere connected with the missing hand, is significantly correlated with phantom limb pain.