How is nerve growth factor related to pain, and what evidence exists for its efficacy and safety?
Nerve growth factor (NGF) is a neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is important in early human development and becomes less important as we age. NGF is upregulated in painful conditions, and binding to the tyrosine receptor kinase A receptor is thought to activate nociceptors; inhibition reverses pain in animal models. Tanezumab and fulranumab are two different monoclonal antibodies to NGF currently in clinical trials. Tanezumab has positive trials in osteoarthritis, chronic low back pain, and cancer. Trials in diabetic peripheral neuropathy, postherpetic neuralgia, and pancreatitis failed to show any effect. A phase III trial in cancer-related pain is currently being conducted outside the United States. Fulranumab has had negative trials in low back pain and osteoarthritis. However, differences in trial design may have resulted in false-negative results, and development is still continuing. The main side effect reported with this class is some abnormal peripheral sensations. Reports of avascular necrosis in the early trials of these drugs resulted in a US Food and Drug Administration (FDA) hold on development. However, it was determined that these adverse events were nonsteroidal antiinflammatory drug (NSAID)-dependent; the hold was lifted and clinical trials have resumed.