BRAF Inhibitors Cut Pain Sensitivity in Preclinical Nerve Injury Models

Preclinical models showed that the BRAF inhibitor vemurafenib and the MEK inhibitor selumetinib reduced sensitivity to touch, pressure, and heat following nerve injury, according to new findings published in Science Signaling on 25 August 2026.

How BRAF connects nerve damage to pain signaling

Chronic nerve pain often persists long after injury and responds poorly to standard medications. Scientists at The University of Texas MD Anderson Cancer Center identified BRAF—a protein previously linked to cancer—as a contributor to pathological pain signaling after nerve damage. Their work suggests BRAF helps initiate, intensify, and sustain pain signals in neuropathic conditions.

In preclinical nerve injury models, BRAF migrated from peripheral sensory nerve cells to their terminals in the spinal cord. There, it activated molecular pathways that increased activity of NMDA receptors—protein channels involved in nerve cell communication. The team also detected a correlation between BRAF-related signaling proteins and NMDA receptors in human spinal cord tissue samples.

Genetic evidence strengthens BRAF’s role

Genetic experiments confirmed BRAF’s involvement in neuropathic pain. Deleting the Braf gene led to less persistent pain sensitivity, while direct activation of BRAF induced pain sensitivity even in models without nerve injury. These opposing outcomes support BRAF’s contribution to both onset and maintenance of neuropathic pain.

The research 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.”

Pathway inhibition and therapeutic implications

Both vemurafenib and selumetinib lowered pain sensitivity in injured models but did not affect normal responses in uninjured controls. The findings remain preclinical. Before human trials for neuropathic pain can begin, researchers must establish appropriate dosing, delivery methods, and safety profiles for BRAF inhibitors in this context. They also aim to determine what triggers BRAF’s movement from peripheral nerves to the spinal cord after injury.

The study, titled “BRAF recruitment to spinal sensory synapses promotes neuropathic pain by potentiating transsynaptic NMDA receptor activity,” was authored by Daozhong Jin, Hong Chen, Yuying Huang, Shao-Rui Chen, and Hui-Lin Pan. It appeared in Science Signaling with DOI: 10.1126/scisignal.aeh6852. Funding came from the National Institutes of Health and the Pamela and Wayne Garrison Distinguished Chair Endowment.