Targeting neurotrophic factors: Novel approaches to musculoskeletal pain

Chronic pain represents a substantial unmet medical need globally. In recent years, the quest for a new generation of novel, safe, mechanism-based analgesic treatments has focused on neurotrophic factors, a large group of secreted proteins that control the growth and survival of different populations of neurons, but that postnatally are involved in the genesis and maintenance of pain, with biological activity in both the periphery and the central nervous system. In this narrative review, we discuss the two families of neurotrophic proteins that have been extensively studied for their role in pain: first, the neurotrophins, nerve growth factor (NGF) and brain-derived growth factor (BDNF), and secondly, the GDNF family of ligands (GFLs). We provide an overview of the pain pathway, and the pain-producing effects of these different proteins. We summarize accumulating preclinical and clinical findings with a focus on musculoskeletal pain, and on osteoarthritis in particular, because the musculoskeletal system is the most prevalent source of chronic pain and of disability, and clinical testing of these novel agents - often biologics- is most advanced in this area.