Neuropilin-1 is a co-receptor for NGF and TrkA-evoked pain.

Although monoclonal antibodies to nerve growth factor (NGF) reduce pain in patients with osteoarthritis, they failed to gain FDA approval due to the deleterious consequences of sequestrating NGF throughout the body. We report that neuropilin 1 (NRP1) is an alternative target for the treatment of NGF-dependent pain. NRP1 and the NGF receptor, tropomyosin-related kinase A (TrkA), are coexpressed in neurons that that detect painful stimuli in humans and mice. NRP1 binds NGF and escorts TrkA to the surface of pain-sensing nerves. NRP1 antagonism prevents NGF-and TrkA-mediated pain. The identification of NRP1 as an NGF receptor that is enriched in pain-sensing nerves reveals an alternate and much-needed target for treatment of the multiple forms of NGF-evoked pain.