HOUSTON, AUGUST 25, 2026 ― Researchers at The University of Texas MD Anderson Cancer Center found new evidence that BRAF, a protein commonly involved in cancer, plays a key role in developing, amplifying and maintaining chronic pain caused by nerve damage. Using BRAF inhibitors reduced pain sensitivity in preclinical models, suggesting the therapeutic potential of this approach for treating chronic nerve pain.
The study, published today in Science Signaling , was co-led by Shao-Rui Chen, M.D. , professor of Anesthesiology and Perioperative Medicine , and Hui-Lin Pan, M.D., Ph.D. , endowed chair of Anesthesiology and Perioperative Medicine.
"Our findings identify the cancer-promoting protein BRAF as a key driver of pathological pain signaling following nerve injury," Pan said. "Because BRAF inhibitors are already approved for cancer treatment, this discovery raises the possibility of rapidly repurposing existing therapies to reduce the level of pain signals entering the spinal cord and improve patient quality of life."
How does nerve injury cause chronic pain?
Chronic nerve pain, or neuropathic pain, can come from injury, disease or even life-saving cancer treatments. This pain can be intense and persistent, and it responds poorly to conventional pain medications, negatively affecting patient quality of life.
Protein channels in the brain and spinal cord, known as NMDA receptors, help nerve cells communicate. After nerve injury, these NMDA receptors can become hyperactive, amplifying pain signals. To identify potential mechanisms, the researchers explored the role of BRAF on NMDA receptor activity.
What did the researchers find in this study?
Using preclinical models of nerve injury, the researchers discovered that BRAF moved from peripheral sensory nerve cells to their terminals inside the spinal cord, where it activated molecular signals to increase NMDA receptor activity. They also found a correlation between BRAF signaling proteins and NMDA receptors in human spinal cord samples.
These initial results suggested that targeting BRAF could help reduce activity in the NMDA receptors to reduce pain.
Does targeting BRAF reduce pain?
In the preclinical models, the BRAF inhibitor vemurafenib and the MEK inhibitor selumetinib reduced sensitivity to touch, pressure and heat but did not change normal response in models without nerve injury.
Deleting the Braf gene also resulted in less persistent pain sensitivity. Conversely, activating BRAF directly caused pain sensitivity in models that did not have nerve injury, highlighting the key role of BRAF in starting and maintaining neuropathic pain.
What does this mean for patients who have nerve injury and chronic pain?
These results are preclinical, and researchers will need to further examine the appropriate dosing, delivery methods and possible side effects of BRAF inhibitors prior to clinical trials in humans. The researchers also hope to understand how nerve injury triggers the translocation of BRAF from the nerves to the spinal cord.
However, these results suggest that BRAF signaling is associated with NMDA receptor activation in the spinal cord and that currently available BRAF inhibitors have therapeutic potential to treat neuropathic pain.
