Progressive neurodegeneration in human dorsal root ganglion from diabetes to painful neuropathy

Diabetic painful neuropathy (DPN) is characterized by neuropathic pain accompanied by loss of sensory function. We hypothesized that neurodegeneration in the dorsal root ganglion (DRG) could underlie DPN progression. To address this question, we performed multi-omic evaluation on DRGs from otherwise healthy organ donors, donors with diabetes but no neuropathy, and donors with clinically diagnosed DPN. We discovered that the first stages of neurodegeneration begin early in diabetes before the onset of DPN, with Nageotte nodule formation accompanied by apoptotic gene expression and decreased proportion of specific populations of A-fibers in DPN with remodeling of non-neuronal cells. Our findings define DPN as a neurodegenerative disorder of the DRG, identify molecular markers of disease stage, and highlight the need for early intervention to prevent irreversible neurodegeneration.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-01-20
DOI
https://doi.org/10.64898/2026.01.16.700028
Primary Topic
Pain Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
0.00

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article

Progressive neurodegeneration in human dorsal root ganglion from diabetes to painful neuropathy

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bioRxiv (Cold Spring Harbor Laboratory)
Pain Mechanisms and Treatments
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Progressive neurodegeneration in human dorsal root ganglion from diabetes to painful neuropathy

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article en

Abstract

Diabetic painful neuropathy (DPN) is characterized by neuropathic pain accompanied by loss of sensory function. We hypothesized that neurodegeneration in the dorsal root ganglion (DRG) could underlie DPN progression. To address this question, we performed multi-omic evaluation on DRGs from otherwise healthy organ donors, donors with diabetes but no neuropathy, and donors with clinically diagnosed DPN. We discovered that the first stages of neurodegeneration begin early in diabetes before the onset of DPN, with Nageotte nodule formation accompanied by apoptotic gene expression and decreased proportion of specific populations of A-fibers in DPN with remodeling of non-neuronal cells. Our findings define DPN as a neurodegenerative disorder of the DRG, identify molecular markers of disease stage, and highlight the need for early intervention to prevent irreversible neurodegeneration.

bioRxiv (Cold Spring Harbor Laboratory)
University of Vienna (AT), The University of Texas MD Anderson Cancer Center (US), The University of Texas at Dallas (US), University of Washington (US), North Texas Regional Center for Innovation and Commercialization (US), Seattle University (US)
Austrian Science Fund, Universität Wien, National Institutes of Health
Good health and well-being
Openalex Percentile: Top 83%
Pain Mechanisms and Treatments
DOIOpen Access PDFOpenAlex
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