BRAF inhibitors reduce pain sensitivity in preclinical models

A light touch, pressure or heat became a stronger signal in models of nerve injury. At The University of Texas MD Anderson Cancer Center, researchers found that BRAF, a protein commonly involved in cancer, helps develop, amplify and maintain the pain that follows nerve damage. Their findings were published in Science Signaling.

The team traced BRAF from peripheral sensory nerve cells to their terminals inside the spinal cord. There, it activated molecular signals that increased NMDA receptor activity; these protein channels help nerve cells communicate and can amplify pain signals after an injury. BRAF signaling proteins also correlated with NMDA receptors in human spinal cord samples.

The intervention worked in preclinical models. The BRAF inhibitor vemurafenib and the MEK inhibitor selumetinib reduced sensitivity to touch, pressure and heat, while leaving normal responses unchanged in models without nerve injury. Deleting the Braf gene reduced persistent pain sensitivity; activating BRAF directly produced pain sensitivity even without nerve injury.

For patients, the concrete promise is a possible new use for medicines that are already approved for cancer treatment, rather than a treatment available today for chronic nerve pain. Neuropathic pain can result from injury, disease or cancer treatments and often responds poorly to conventional pain medicines, so a drug-repurposing route could matter if the effect survives human testing.

That test has not happened yet. The researchers still need to determine dosing and delivery methods, assess possible side effects and explain how nerve injury triggers BRAF’s movement toward the spinal cord before clinical trials in humans can begin. The current evidence identifies a target and a pair of candidate drugs—not a proven pain therapy.