Summary: Researchers at The University of Texas at Dallas’ Center for Advanced Pain Studies (CAPS) have identified a long-overlooked cellular structure, the Nageotte nodule, as a prominent and potentially driving feature of diabetic peripheral neuropathy. Found in abundance in sensory dorsal root ganglia (DRG) from donors with diabetes, these nodules represent clusters of degraded sensory neurons and supporting glial cells and are associated with sprouting, pain-sensing axons. The discovery points toward new opportunities for early neuroprotective treatment to prevent or reduce diabetic nerve pain.
Key Facts:
- Rediscovered marker: Nageotte nodules, first described in 1922, are abundant in DRG tissue from people with diabetes and diabetic neuropathy.
- Pain-related pathology: The nodules contain sprouting sensory axons and neuroma-like fibers that may generate spontaneous pain signals.
- Therapeutic implication: Preventing early neurodegeneration in the DRG could stop nodule formation and reduce neuropathic pain.
Source: UT Dallas
New research published in Nature Communications documents a clear association between diabetic peripheral neuropathy (DPN) and Nageotte nodules—clusters of non-neuronal cells that form where sensory neurons have died. The study examines human dorsal root ganglia collected from organ donors and combines histology with spatial transcriptomics to characterize these structures at the molecular level.
Diabetic neuropathy affects millions and commonly produces sharp, shooting pain in the hands and feet. Current treatment options are limited, and progressive loss of peripheral nerve function can lead to severe complications, including loss of sensation and, in extreme cases, amputation. By identifying a reproducible anatomical and molecular lesion in affected sensory ganglia, the study opens a path to new diagnostic markers and therapeutic strategies.
In this study, CAPS investigators examined DRG tissue from a large cohort of organ donors. They found that Nageotte nodules were much more common in donors with diabetes—and especially in those with documented diabetic neuropathy—than in donors without diabetes. Where sensory neurons had degenerated, the nodules were dominated by satellite glia and non-myelinating Schwann cells. Intertwined within many nodules were dystrophic axons positive for peripherin and Nav1.7, forming small neuroma-like bundles that likely arise from neighboring sensory neurons.
Lead researchers emphasize two important points. First, Nageotte nodules are not merely incidental histological oddities; they appear to be an integral feature of DRG neurodegeneration in DPN. Second, the associated sprouting axons are predominantly pain-sensing fibers, suggesting a direct mechanism for neuropathic pain: injured or degenerating neurons in the ganglion produce aberrant axonal growth and spontaneous activity that can generate chronic pain signals.
“Our data indicate that neurodegeneration inside the dorsal root ganglion is a core element of diabetic neuropathy,” said Dr. Ted Price, CAPS director and co-corresponding author. “Recognizing this should shift attention to early neuroprotective strategies that prevent nodule formation before irreversible damage and persistent pain pathways develop.”
Co-corresponding author Stephanie Shiers, who identified the nodules in multiple DRG samples, noted the historical neglect of these structures. First described by Jean Nageotte in 1922, nodules have rarely been studied in the past century. Using modern molecular methods, the team showed that nodules account for a substantial portion of neuronal loss in affected ganglia and carry transcriptional signatures consistent with reactive glia and degenerating axons.
The research leveraged a sizeable human tissue resource through collaboration with organ donation organizations, enabling analysis across a diverse set of donors. Unlike many prior reports that were limited to single cases, this study examined tissue from 90 donors, providing statistical weight to the association between diabetes, neuropathy, and Nageotte nodules.
Practical implications include new targets for therapeutic development. If nodules form after early neuronal injury, treatments that protect sensory neurons or modulate glial responses might prevent axonal sprouting and reduce pain. The discovery also suggests that profiling DRG pathology could improve diagnosis and staging of diabetic neuropathy and guide personalized interventions.
The research team includes multiple investigators from the UT Dallas Department of Neuroscience and collaborators from the Southwest Transplant Alliance and The University of Adelaide. Authors cited that Nageotte nodules in DPN accounted for a notable proportion of neuronal loss in affected ganglia and that invading peripherin- and Nav1.7-positive axons form neuroma-like structures within these nodules, findings consistent with a role in neuropathic pain generation.
Funding: Supported by the National Institute of Neurological Disorders and Stroke through grants U19NS130608 and R01NS111929.
About this neuropathic pain research news
Author: Stephen Fontenot
Source: UT Dallas
Contact: Stephen Fontenot, UT Dallas
Image credit: Neuroscience News
Original Research (open access): “Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy” by Ted Price et al., Nature Communications. DOI: 10.1038/s41467-025-59538-z
Abstract
Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy
Nageotte nodules are clusters of non-neuronal cells that form after sensory neuron death. Historically noted but poorly characterized, their molecular identity and role in neuropathies have been unclear. This study molecularly characterizes Nageotte nodules from DRG tissue of organ donors with diabetic peripheral neuropathy. The authors show that Nageotte nodules are abundant in DPN sensory ganglia, accounting for a significant portion of neuronal loss. Dystrophic axons positive for peripherin and Nav1.7 invade these nodules and form small neuroma-like structures. Histology and spatial sequencing reveal that nodules are predominantly composed of satellite glia and non-myelinating Schwann cells expressing SPP1, intertwined with sprouting sensory axons originating from neighboring neurons. These findings position Nageotte nodules as an integral feature of DRG neurodegeneration and suggest potential targets for sensory neuron protection and improved pain management in DPN.