Rediscovered Cell Clusters Could Be Key to Understanding Diabetic Neuropathy Pain

A century-old phenomenon that has largely been overlooked may play a pivotal role in diabetic pain management, according to recent research conducted at the University of Texas at Dallas' Center for Advanced Pain Studies (CAPS).

The study, published in Nature Communications, reveals that clusters of cells known as Nageotte nodules are significant indicators of nerve cell death within human sensory ganglia. These findings suggest that targeting these nodules could lead to the development of new medications aimed at protecting nerves or managing the symptoms of diabetic neuropathy.

Diabetic neuropathy is one of the most prevalent forms of neuropathic pain, affecting approximately 11 million individuals in the United States alone, according to the Centers for Disease Control and Prevention. This condition typically manifests as severe pain in the extremities and can lead to debilitating consequences if not managed effectively.

Research scientist Stephanie Shiers, a co-author of the study, emphasized the urgent need for better treatment options, stating that untreated diabetic neuropathy can result in significant health risks, including the possibility of amputation due to extensive nerve damage.

The CAPS team is currently mapping human dorsal root ganglia and other sensory tissues to uncover the underlying mechanisms of pain. Shiers noted an unexpected prevalence of Nageotte nodules in tissue samples obtained from organ donors with diabetes. The discovery of these nodules in a substantial number of samples was a significant breakthrough for the research team.

Nageotte nodules consist of decayed sensory neurons, leaving behind clusters of non-neuronal cells. Initially documented in 1922 by French neuroanatomist Jean Nageotte, these nodules have received scant attention in the scientific literature over the past century, appearing in only about 20 studies, many of which are outdated.

Shiers pointed out that these nodules likely indicate degeneration as a result of hyperglycemia, which impacts neuron viability. Very little is known about their molecular composition, and they have not been widely recognized within the pain research community.

The study aimed to characterize these nodules at a molecular level. Through advanced histological techniques and spatial sequencing, researchers found that Nageotte nodules are abundant in sensory ganglia affected by diabetic neuropathy, primarily composed of satellite glial cells and non-myelinating Schwann cells.

Shiers observed that within these nodules, sensory neuron axons appeared to sprout, resembling little neuromas. This abnormal axon growth could be linked to the pain associated with diabetic neuropathy. The research indicates a unique pathological state that has not been previously described in humans.

While past studies on Nageotte nodules have typically focused on individual cases, this research utilized samples from a diverse group of 90 individuals. The identification of axonal sprouting in this context marks a novel contribution to the understanding of sensory neurons.

Researchers attribute the ability to study human dorsal root ganglia from such a large cohort to the efforts of the Southwest Transplant Alliance, a nonprofit organization dedicated to organ donation and transplantation.

According to the President and CEO of the Southwest Transplant Alliance, the ability to contribute to significant medical advancements through organ donation serves as a source of hope for families who have experienced loss.

The findings from this research not only challenge existing perceptions of diabetic neuropathy but also highlight the need for a shift in treatment strategies. In light of these discoveries, there is a growing emphasis on neuroprotective approaches during the early stages of the disease to prevent the formation of Nageotte nodules.