Abstract

Nerve Growth Factor (NGF) and its cognate receptor tropomyosin receptor kinase A (TrkA) have been linked to the hypersensitization and pain associated with many human disease conditions. The interplay of the NGF / TrkA axis with the immune modulatory system in human disease has been less well studied. Rheumatoid arthritis (RA) is a polyarthritis, immune-mediated disease and has recently been shown to have increased expression of NGF and the TrkA receptor in diseased joints. Synovitis and the destruction of cartilage leading to chronic pain are hallmarks of human RA. It is clear that inflammation plays a significant role in the pathogenesis of joint destruction, but less clear is the role that NGF and TrkA play in this process. The rat collagen-induced arthritis model provides the opportunity to study the role of NGF and TrkA in a relevant animal model of RA. The TrkA selective inhibitors tested showed significant reduction of pain in the model as well as surprising disease reduction for endpoints of joint destruction.