Now, researchers at Duke University School of Medicine say restoring healthy mitochondria could offer a completely new way to treat that pain.

In a study published in Nature, the team used both human tissue and mouse models to test whether replenishing mitochondria could help damaged nerve cells recover. The treatment significantly reduced pain linked to diabetic neuropathy and chemotherapy-related nerve damage. In some cases, the relief lasted for up to 48 hours.

Rather than simply blocking pain signals, the researchers believe the approach may address one of the underlying causes of chronic nerve pain by restoring the energy supply nerve cells need to function properly.

"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."

Healthy Mitochondria Helped Nerves Recover

The findings add to growing evidence that cells can transfer mitochondria to one another. Scientists are increasingly viewing this process as a natural support system that may play a role in conditions ranging from obesity and cancer to stroke and chronic pain.

The Duke researchers focused on satellite glial cells, which surround and support sensory neurons. The study uncovered a previously unknown role for these cells. According to the researchers, satellite glial cells appear to pass healthy mitochondria directly into sensory neurons through tiny structures known as tunneling nanotubes.

When this transfer process breaks down, nerve fibers begin to deteriorate, Ji explained. That damage can trigger symptoms such as pain, tingling, and numbness, especially in the hands and feet where nerve fibers extend 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.

When researchers increased this mitochondrial transfer in mice, pain-related behaviors dropped by as much as 50%.

Scientists Identified a Key Protein Behind the Process

The team also tested a more direct method by injecting isolated mitochondria from both humans and mice into the dorsal root ganglia, clusters of nerve cells that send sensory information to the brain.

The results depended heavily on the quality of the mitochondria. Healthy donor mitochondria reduced pain, while mitochondria taken from people with diabetes produced no benefit.

Researchers also identified a protein called MYO10 as critical for creating the tunneling nanotubes that allow mitochondria to move between cells.

Ji worked alongside lead author Jing Xu, PhD, a research scholar in the Department of Anesthesiology, as well as longtime collaborator Caglu Eroglu, PhD, a Duke professor of cell biology known for her work studying glial cells.

A Potential New Direction for Chronic Pain Treatment

The researchers say more studies are still needed, including high resolution imaging to better understand exactly how the nanotubes deliver mitochondria within living nerve tissue.

Even so, the findings point to a previously overlooked communication system between nerve cells and glial cells that could eventually lead to treatments targeting chronic pain at its source instead of simply masking symptoms.