Millions of people live with chronic nerve pain, where even the slightest touch can feel intense and excruciating. Scientists have long suspected that this type of pain begins when mitochondria, the tiny energy-producing structures in cells, stop working properly in damaged nerves.
Now, researchers at Duke University School of Medicine say restoring healthy mitochondria may offer an entirely new way to treat that pain.
In a study published in naturethe research team used both human tissue and mouse models to test whether mitochondrial replenishment could help damaged nerve cells recover. This treatment significantly reduced pain associated with diabetic neuropathy and chemotherapy-related nerve damage. In some cases, symptom relief lasted up to 48 hours.
Researchers believe this approach could address one of the root causes of chronic nerve pain by restoring the energy supply nerve cells need to function properly, rather than simply blocking pain signals.
“By giving fresh mitochondria to damaged nerves or helping nerves make more of their own mitochondria, we can reduce inflammation and support healing,” said Ru-Rong Ji, Ph.D., lead author of the study and director of the Center for Translational Pain Medicine in the Department of Anesthesiology at Duke School of Medicine. “This approach has the potential to reduce pain in an entirely new way.”
Healthy mitochondria help nerve recovery
This finding adds to the evidence that cells can communicate mitochondria to each other. Scientists are increasingly seeing 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. This study reveals a previously unknown role for these cells. According to the researchers, satellite glial cells appear to pass healthy mitochondria directly to sensory neurons through tiny structures known as tunneling nanotubes.
When this transmission process breaks down, the nerve fibers begin to deteriorate, Ji explained. That damage can cause symptoms such as pain, tingling, and numbness, especially in the limbs where the nerve fibers extend the farthest.
“Satellite glial cells may help protect neurons from pain by sharing energy stores,” 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 decreased by as much as 50%.
Scientists have identified the key protein behind the process
The researchers also tested a more direct method, injecting mitochondria isolated from both humans and mice into the dorsal root ganglion, a collection of nerve cells that send sensory information to the brain.
The results were highly dependent on mitochondrial quality. Mitochondria from healthy donors reduced pain, but mitochondria from diabetic patients had no effect.
The researchers also identified a protein called MYO10 that is important for the creation of tunnel nanotubes that allow mitochondria to move between cells.
Ji collaborated on the study with lead author Dr. Jing Xu, a researcher in the Department of Anesthesiology, and longtime collaborator Dr. Caglu Eroticu, a professor of cell biology at Duke University known for his work on glial cells.
Potential new directions for chronic pain treatment
The researchers say further research is still needed, including high-resolution imaging to understand exactly how the nanotubes deliver mitochondria into living neural tissue.
Still, the findings point to a previously overlooked communication system between neurons and glial cells that could ultimately lead to treatments that target the causes of chronic pain rather than simply masking the symptoms.
