• Martin Schmelz, Patrick Mantyh, Anne-Marie Malfait, John Farrar, Tony Yaksh, Leslie Tive, and Lars Viktrup.
• Department of Experimental Pain Research Mannheim, University of Heidelberg, Heidelberg, Germany.
• Pain. 2019 Oct 1; 160 (10): 2210-2220.

AbstractChronic pain continues to be a significant global burden despite the availability of a variety of nonpharmacologic and pharmacologic treatment options. Thus, there is a need for new analgesics with novel mechanisms of action. In this regard, antibodies directed against nerve growth factor (NGF-Abs) are a new class of agents in development for the treatment of chronic pain conditions such as osteoarthritis and chronic low-back pain. This comprehensive narrative review summarizes evidence supporting pronociceptive functions for NGF that include contributing to peripheral and central sensitization through tropomyosin receptor kinase A activation and stimulation of local neuronal sprouting. The potential role of NGF in osteoarthritis and chronic low-back pain signaling is also examined to provide a mechanistic basis for the observed efficacy of NGF-Abs in clinical trials of these particular pain states. Finally, the safety profile of NGF-Abs in terms of common adverse events, joint safety, and nerve structure/function is discussed.

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