Chronic nerve pain, or neuropathic pain, can persist for months or years after the initial injury or illness and often does not respond well to standard pain medications. Now, researchers at The University of Texas MD Anderson Cancer Center have identified a protein that may play a key role in this persistent pain, opening the door to a potential new treatment approach using existing cancer drugs.
The study, published inScience Signaling, focused on BRAF, a protein already known for its involvement in cancer. The researchers found that after nerve damage, BRAF travels along sensory nerve cells to their endings in the spinal cord, where it activates signaling that increases the activity of NMDA receptors. These receptors, protein channels in the brain and spinal cord that help nerve cells communicate, can become excessively active after nerve damage and amplify pain signals traveling to the brain.
In experiments using preclinical models, drugs that inhibit BRAF signaling reduced pain sensitivity. This finding is particularly significant because BRAF inhibitors are already approved for cancer treatment, raising the possibility of repurposing these therapies for chronic nerve pain.
“Our findings identify the cancer-promoting protein BRAF as a key driver of pathological pain signaling following nerve injury,” said Hui-Lin Pan, , , endowed chair of Anesthesiology and Perioperative Medicine at MD Anderson and co-leader of the study. “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.”
The research was co-led by Shao-Rui Chen, , professor of Anesthesiology and Perioperative Medicine, and Pan. The team had previously shown that chemotherapy-induced neuropathic pain involves changes in NMDA receptor activity, and this study extends that work to understand how nerve damage leads to persistent pain.
The findings also highlight the link between BRAF-related proteins and NMDA receptors in human spinal cord tissue, suggesting the mechanism may be relevant to human pain conditions.
Despite the promise, the researchers caution that this is early research. The findings have not yet established BRAF inhibitors as a treatment for chronic nerve pain in people. The next step is determining whether blocking BRAF can safely and reliably reduce pain in human patients. If clinical studies confirm the findings, BRAF-directed treatment could eventually offer a new strategy for difficult-to-control nerve pain.
Neuropathic pain can arise from various causes, including injury, disease, or medical treatments. For example, chemotherapy-induced peripheral neuropathy—a common side effect of some cancer treatments—can cause symptoms such as burning pain, tingling, numbness, sensitivity to touch, and shooting or electric shock-like sensations. Many patients find conventional pain medications provide limited relief, making new treatment options particularly valuable.
The study adds to a growing body of research aimed at understanding the molecular mechanisms underlying chronic pain, with the hope of developing more effective therapies.
This article is based on reporting from India Today and Times