Stanford University School of Medicine researchers have identified a previously unknown protein, PRGF-3, that plays a central role in why some patients develop chronic pain while others recover fully from the same injury. The protein appears to lock pain signaling pathways in an active state, preventing the nervous system from naturally downregulating pain responses after the initial injury heals.
The discovery was made through a combination of proteomics analysis and patient-derived dorsal root ganglion tissue samples. Patients with fibromyalgia, complex regional pain syndrome, and post-surgical chronic pain showed PRGF-3 levels three to seven times higher than pain-free controls.
A small molecule inhibitor targeting PRGF-3 has already shown efficacy in rodent models, eliminating chronic pain behaviors without affecting the animals' acute pain responses — meaning they could still detect new injuries normally. Human trials are expected to begin in Q3 2025, with researchers cautiously optimistic about a non-opioid therapeutic pathway.