Fig. 1: Identification of Nageotte nodules in DRGs from diabetic organ donors.

A Hematoxylin and eosin staining was performed on DRGs from organ donors (n = 90), B and then each DRG was scored for prevalence of Nageotte nodules using a qualitative scoring system. C After scoring, donors were grouped based on their medical history of diabetes, analgesic usage, or medical note of diabetic peripheral neuropathy (DPN). Diabetic donors had significantly higher Nageotte nodule scores compared to non-diabetic donors without pre-existing pain conditions. In diabetics, Nageotte nodule content increased in severity in relation to DPN as indicated by analgesic usage, medical note of DPN, and/or diabetes-related amputation. D Representative images of an L4 bi-ganglia from a DPN donor immunostained for GFAP (red, satellite glial cells and non-myelinating Schwann cells), peripherin (green, sensory neurons), and DAPI (blue, nuclei). Asterisks denote Nageotte nodules. Sample size: Non-diabetic n = 7; DPN n = 9. E The percentage of Nageotte nodules was significantly higher in the DPN DRGs (average: 25%) compared to non-diabetic DRGs (average: 8%). F Confocal image of a peripherin-positive axon bundle intertwined with other cells at a Nageotte nodules. Similar staining was observed across all 9 DPN donors. G Image taken from Jean Nageotte’s original 1922 publication¹ in which three Nageotte nodules (mid top, mid bottom, and left) contain axon bundles which sprout from a glomerulus (middle). H) Transmission electron microscopy (TEM) of a Nageotte nodule. Arrows point to unmyelinated axonal fibers. Sample size: Diabetic taking analgesics n = 2. Statistical tests: (C): One-way ANOVA with Bonferroni’s multiple comparisons test. *p = 0.0309, ****p < 0.0001, ns (not-significant) p = 0.5525. E: Unpaired two-sided t-test. **p = 0.0013. Data points represent individual donors. Error bars = mean +/- SEM. Scale bars: (A): 500 μm, 100 μm. 20 μm (B): 100 μm. (D): Mosaic—1 mm and other panels—50 μm. (F): 10 μm. (H): 2 μm.