Structural Brain Alterations in Key Somatosensory and Nociceptive regions in Diabetic Peripheral Neuropathy.
Despite increasing evidence demonstrating structural and functional alterations within the central nervous system in diabetic peripheral neuropathy (DPN), the neuroanatomical correlates of Painful- and Painless-DPN have yet to be identified. Focusing on structural magnetic resonance (MR) imaging, the aims of this study were to 1) define the brain morphological alterations in Painful- and Painless-DPN and 2) explore the relationships between brain morphology and clinical/neurophysiological assessments.
Research Design and Methods
277 participants with type 1 and 2 diabetes (No-DPN [n=57]; Painless-DPN [n=77]; and Painful-DPN [n=77]) and 66 healthy volunteers (HV) were enrolled. All underwent detailed clinical/neurophysiological assessment and brain MR imaging at 3-Tesla. Painful-DPN participants were subdivided into the irritable nociceptor (IR) and the non-irritable nociceptor (NIR) phenotype using the German Research Network on Neuropathic Painprotocol. Cortical reconstruction and volumetric segmentation were performed with FreeSurfer software and voxel-based morphometry implemented in FSL.
Both Painful- and Painless-DPN had significant reduction in primary somatosensory and motor cortical thickness compared to HV and No-DPN [P=0.02; F(3,275)=3.36 and P=0.01; F(3,275)=3.80 respectively]. Somatomotor cortical thickness correlated with neurophysiological measures of DPN severity. There was also reduction in ventrobasal thalamic nuclei volume in both Painless- and Painful-DPN. Painful-DPN subjects with the NIR nociceptor phenotype had reduced primary somatosensory, posterior cingulate cortical and thalamic volume compared to the IR nociceptor phenotype.
In this, the largest neuroimaging study in DPN to date, we have demonstrated significant structural alterations in key somatomotor/nociceptive brain regions specific to Painless-DPN and Painful-DPN including the IR and NIR nociceptor phenotype.