Structural Brain Alterations in Key Somatosensory and Nociceptive Regions in Diabetic Peripheral Neuropathy

Author:

Selvarajah Dinesh1ORCID,Sloan Gordon2,Teh Kevin3ORCID,Wilkinson Iain D.3ORCID,Heiberg-Gibbons Francesca1,Awadh Mohammad1,Kelsall Alan2,Grieg Marni2,Pallai Shillo2,Tesfaye Solomon2ORCID

Affiliation:

1. 1Department of Oncology and Metabolism, Medical School, The University of Sheffield, Sheffield, U.K.

2. 3Diabetes Research Department, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, U.K.

3. 2Academic Department of Magnetic Resonance Imaging, The University of Sheffield, Sheffield, U.K.

Abstract

OBJECTIVEDespite 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.RESEARCH DESIGN AND METHODSA 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.RESULTSBoth 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.CONCLUSIONSIn 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.

Funder

Knowledge Exchange Support Fund, University of Sheffield

Efficacy and Mechanism Evaluation Programme

European Foundation for the Study of Diabetes

Publisher

American Diabetes Association

Subject

Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine

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