Researchers at The University of Texas MD Anderson Cancer Center have found evidence that BRAF, a protein involved in cancer, plays a central role in developing and maintaining chronic pain caused by nerve damage. A study published in Science Signaling showed that BRAF inhibitors reduced pain sensitivity in preclinical models.
Chronic nerve pain, or neuropathic pain, can result from injury, disease or cancer treatments and often resists conventional pain medications. The researchers explored how BRAF affects NMDA receptors, protein channels in the brain and spinal cord that allow nerve cells to communicate. After nerve injury, these receptors can become overactive, amplifying pain signals.
Using preclinical models of nerve injury, the researchers discovered that BRAF moved from sensory nerve cells to their terminals in the spinal cord, where it activated signals to increase NMDA receptor activity. They also found a correlation between BRAF signaling proteins and NMDA receptors in human spinal cord samples.
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 responses in models without nerve injury. Deleting the Braf gene also resulted in less persistent pain sensitivity, while activating BRAF directly caused pain sensitivity in uninjured models.
The researchers noted that further work is needed to examine appropriate dosing, delivery methods and possible side effects of BRAF inhibitors before clinical trials in humans. However, the study suggests that currently available BRAF inhibitors have potential to treat neuropathic pain.
