Discovering a New Receptor for Nerve Growth Factor: Nigel Bunnett, PhD, BSc

WATCH TIME: 4 minutes

"By identifying targets enriched in nociceptors, we hope to avoid the side effects associated with systemic sequestration of nerve growth factor."

Chronic pain is one of the costliest health problems in the U.S, leading to increased medical expenses, lost income, lost productivity, compensation payments, and legal charges. This condition persists beyond the usual recovery period or occurs along with a chronic health condition, such as arthritis. Medical management of chronic pain includes over-the-counter medicines such as nonsteroidal anti-inflammatory drugs, aspirin, or acetaminophen, as well as prescription pain medicines such as opioids.

Researchers have worked tirelessly to identify new pathways to target chronic pain and ultimately provide greater relief for patients who experience this condition. One recent study from those at NYU Langone’s Pain Research Center identified a new receptor for nerve growth factor (NGF) that plays an important role in pain signaling, even though it does not signal on its own. Through a series of studies using mouse and human neurons, researchers discovered neuropillin-1 (NRP1), a protein expressed in neurons and other cells types. Further molecular modeling suggested that 2 molecules of NGF, 2 molecules of TrkA, and 2 molecules of NRP1 together form a pain signaling complex.

Led by Nigel Bunnett, PhD, BSc, researchers then identified a protein, G Alpha Interacting Protein C-terminus 1 (GIPC1), that appears to play a critical role in connecting TrkA and NRP1 and signaling pain. Bunnett, a professor and chair of the Department of Molecular Pathobiology at NYU Langone, recently sat down with NeurologyLive^® to discuss the research, and its significance on future chronic pain drug development. In the interview, he gave clinical insight on the specific findings observed, and why they could lead to safer treatments that avoid side effect seen with monoclonal antibodies that target NGF.

REFERENCE
1. Peach CJ, Tonello R, Damo E, et al. Neuropillin-1 inhibition suppresses nerve-growth factor signaling and nociception in pain models. Journal of Clin Investig. Published online November 26, 2024. doi:10.1172/JCI183873