A hopeful new path may be emerging for millions of people who live with chronic nerve pain, a condition that can turn even a gentle touch into severe discomfort.
For years, scientists have suspected that this pain may be linked to struggling mitochondria, the tiny energy-producing structures inside cells. When nerves are damaged, these mitochondria may stop working as they should, leaving nerve cells without the support they need.
Now, researchers at Duke University School of Medicine have found encouraging evidence that restoring healthy mitochondria may help damaged nerves recover and reduce pain in a fresh and promising way.
In a study published in Nature, the Duke team examined human tissue and mouse models to learn whether adding healthy mitochondria could improve nerve cell function. The results were uplifting: the approach significantly eased pain associated with diabetic neuropathy and nerve damage caused by chemotherapy. In some cases, the benefit lasted as long as 48 hours.
Unlike treatments that mainly block pain signals, this method may work by helping repair one of the deeper problems behind chronic nerve pain: the loss of energy support inside injured nerves.
"By giving damaged nerves fresh mitochondria -- or helping them make more of their own -- we can reduce inflammation and support healing," said the study's senior author Ru-Rong Ji, PhD, director of the Center for Translational Pain Medicine in the Department of Anesthesiology at Duke School of Medicine. "This approach has the potential to ease pain in a completely new way."
Support Cells May Share Healthy Energy With Nerves
The study adds to a growing and exciting area of research showing that cells can share mitochondria with one another. Scientists are increasingly seeing this exchange as a helpful biological support system that may matter in many conditions, including obesity, cancer, stroke, and chronic pain.
The Duke researchers paid special attention to satellite glial cells. These cells surround sensory neurons and help support them. The team discovered that satellite glial cells may have an important role that was not previously understood: they appear to deliver healthy mitochondria directly into sensory neurons.
This delivery seems to happen through tiny bridge-like structures called tunneling nanotubes. When this transfer system works well, nerve cells may receive the energy support they need. When it breaks down, Ji explained, nerve fibers can begin to decline. That damage may lead to pain, tingling, and numbness, especially in the hands and feet, where nerve fibers stretch the farthest.
"By sharing energy reserves, satellite glial cells may help keep neurons out of pain," said Ji, a professor of anesthesiology, neurobiology and cell biology at Duke School of Medicine.
In mouse studies, boosting this transfer of mitochondria reduced pain-related behaviors by as much as 50%, giving researchers an encouraging sign that the process may be meaningful for future treatment strategies.
Healthy Mitochondria Made the Difference
The scientists also explored a more direct approach. They injected isolated mitochondria from humans and mice into the dorsal root ganglia, which are clusters of nerve cells that carry sensory messages to the brain.
The outcome depended strongly on mitochondrial health. Mitochondria from healthy donors reduced pain, while mitochondria taken from people with diabetes did not provide the same benefit.
The team also identified a key protein, MYO10, that appears to be essential for forming the tunneling nanotubes that allow mitochondria to travel between cells.
Ji worked with lead author Jing Xu, PhD, a research scholar in the Department of Anesthesiology, and longtime collaborator Caglu Eroglu, PhD, a Duke professor of cell biology recognized for her research on glial cells.
A Bright Direction for Pain Research
More work is still needed before this approach can be developed into a treatment. The researchers say future studies should include high-resolution imaging to show exactly how tunneling nanotubes move mitochondria inside living nerve tissue.
Still, the findings reveal a kind of helpful communication between glial cells and nerve cells that had been largely overlooked. By focusing on restoring nerve health rather than only quieting symptoms, this research offers a hopeful step toward new ways of treating chronic pain at its source.
