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 MRI, 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.

A total of 277 participants with type 1 and 2 diabetes (no DPN [n = 57], painless DPN [n = 77], painful DPN [n = 77]) and 66 healthy volunteers (HVs) were enrolled. All underwent detailed clinical/neurophysiological assessment and brain 3T MRI. Participants with painful DPN were subdivided into the irritable (IR) nociceptor and nonirritable (NIR) nociceptor phenotypes using the German Research Network on Neuropathic Pain protocol. Cortical reconstruction and volumetric segmentation were performed with FreeSurfer software and voxel-based morphometry implemented in FSL.

Both participants with painful and painless DPN showed a significant reduction in primary somatosensory and motor cortical thickness compared with HVs (P = 0.02; F[3,275] = 3.36) and participants with no DPN (P = 0.01; F[3,275] = 3.80). Somatomotor cortical thickness correlated with neurophysiological measures of DPN severity. There was also a reduction in ventrobasal thalamic nuclei volume in both painless and painful DPN. Participants with painful DPN with the NIR nociceptor phenotype had reduced primary somatosensory cortical, posterior cingulate cortical, and thalamic volume compared with the IR nociceptor phenotype.

In this largest neuroimaging study in DPN to date, we demonstrated significant structural alterations in key somatomotor/nociceptive brain regions specific to painless DPN and painful DPN, including the IR and NIR nociceptor phenotypes.