Cancer Drugs Could Be Repurposed to Treat Chronic Nerve Pain, Study Finds

Researchers at the University of Texas MD Anderson Cancer Center have 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. In preclinical models, BRAF inhibitors reduced pain sensitivity, suggesting the drugs could be repurposed to treat chronic nerve pain. The study, co-led by Shao-Rui Chen and Hui-Lin Pan, professors of anesthesiology and perioperative medicine at MD Anderson, is published in Science Signaling.

Chronic nerve pain, also called neuropathic pain, can result from injury, disease or even life-saving cancer treatments, and it responds poorly to conventional pain medications. Protein channels called NMDA receptors help nerve cells communicate in the brain and spinal cord, and after nerve injury these receptors can become hyperactive, amplifying pain signals. To find out what drives this, the researchers examined the role of BRAF in NMDA receptor activity.

Using preclinical models of nerve injury, the researchers found that BRAF moved from peripheral sensory nerve cells to their terminals inside the spinal cord, where it activated molecular signals that increased NMDA receptor activity; they also found a correlation between BRAF signaling proteins and NMDA receptors in human spinal cord samples. "Our findings identify the cancer-promoting protein BRAF as a key driver of pathological pain signaling following nerve injury," said Pan. "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."

In the preclinical models, the BRAF inhibitor vemurafenib and the MEK inhibitor selumetinib reduced sensitivity to touch, pressure and heat without changing normal responses in models that had no nerve injury. Deleting the Braf gene also reduced persistent pain sensitivity, while directly activating BRAF caused pain sensitivity even in models without nerve injury.

The results are preclinical, and researchers say further work is needed to determine appropriate dosing, delivery methods and possible side effects of BRAF inhibitors before testing them in clinical trials in humans.