Different types of nerves respond differently to damage caused by diabetes, with sural nerves showing changes in blood vessel function and increased immune cell activity, and tibial nerves showing more signs of attempted nerve repair.Diabetic peripheral neuropathy, a condition in which diabetes mellitus damages nerves in the body leading to chronic pain, affects roughly 37 million people in the United States and 460 million people worldwide. As diabetic neuropathy progresses, scar tissue forms within the nerve, and protective nerve structures like the perineurium and Schwann cells were shown to become abnormal, leading to irreversible nerve damage and loss of function.

In a new study published in The Journal of Clinical Investigation, Eroboghene Ubogu, M.D., professor in the University of Alabama at Birmingham Department of Neurology and director of the Division of Neuromuscular Diseases, along with researchers from the University of Texas at Dallas and UT Southwestern Medical Center, uncovered several unprecedented findings about how diabetes damages peripheral nerves and causes chronic pain.

Analyzing molecular changes in two types of peripheral nerves that are affected in diabetic peripheral neuropathy – the sural, which carry sensory signals, and the tibial, which carry both sensory and motor signals – researchers aimed to identify the causes of nerve fiber deterioration and chronic pain in diabetic peripheral neuropathy.

The study found that diabetic peripheral neuropathy leads to increased inflammation and immune system activity, which disrupts how effectively nerves send sensory signals to the brain. Of note, different types of nerves respond differently to damage caused by diabetes, with sural nerves showing changes in blood vessel function and increased immune cell activity, and tibial nerves showing more signs of attempted nerve repair.

“Despite significant knowledge on the damage diabetes causes to human peripheral nerves and some clues obtained from studying diabetic mice and rats, the precise changes in the peripheral nerve molecules that cause nerve fiber breakdown and chronic pain are unknown,” Ubogu said. “My collaborators in Texas and I were inspired to use significant advances in studying human molecules in cells and tissues to answer this question.”

Researchers found that human peripheral nerves store messenger RNA and RNA-binding proteins, which help them quickly adapt to stress or injury — a previously unknown mechanism for how nerves respond to damage.

“We had relatively little knowledge about the adult human peripheral nerve molecules when healthy or what changes with specific nerve diseases,” Ubogu said. “Chronic neuropathic pain affects up to 10 percent of all people at a stage during their lifetimes, so studying peripheral nerves is essential to figuring out how to more precisely treat pain.”

Ubogu and the research team hope the results of this recent study will help to better inform medical providers about diabetic peripheral neuropathy, resulting in improved treatment options for patients and continued research advancements on the topic.

“Our future goal is to confirm how the cells and molecules that significantly contribute to nerve fiber breakdown and chronic pain in diabetic peripheral neuropathy do so,” Ubogu said. “We also have the goal to harness the information from this study to guide peripheral nerve repair treatments that could prevent nerve fiber loss, as well as identify avenues for more effective treatments for neuropathic pain in diabetic patients.”