Researchers at the NYU Pain Research Center have made a groundbreaking discovery by identifying a new receptor for nerve growth factor that plays a crucial role in pain signaling. This finding, detailed in a study published in the Journal of Clinical Investigation, opens up new possibilities for developing innovative treatments for conditions like arthritis and various forms of inflammatory and cancer-related pain. Importantly, these new treatments aim to address pain without the side effects that have plagued recent therapies and led to their failure in clinical trials.
“Nerve growth factor is a key player in pain signaling and has been validated as a target for pain management by patients themselves,” explained Nigel Bunnett, the senior author of the study and professor at NYU College of Dentistry. “Our goal was to find safer, non-opioid therapies for chronic pain conditions like arthritis.”
Nerve growth factor is a protein that promotes the growth of neurons and is a potent driver of pain. When released by cells in injured or diseased tissue, it binds to a receptor known as tropomyosin receptor kinase A (TrkA) to transmit pain signals. Monoclonal antibodies, which mimic natural antibodies and target specific proteins, have emerged as a promising treatment for chronic pain by sequestering nerve growth factor. While these antibodies showed promise in clinical trials for relieving osteoarthritis pain, some patients experienced worsened joint damage, leading to the treatments not being approved.
Through a series of studies using mouse and human neurons, the researchers identified neuropilin-1 (NRP1) as a new receptor for nerve growth factor. Expressing high affinity for nerve growth factor, NRP1 was found to bind to the protein and regulate pain signaling, acting as a co-receptor alongside TrkA. Further investigations revealed that NRP1 enhances the local concentration of nerve growth factor presented to TrkA and aids in transporting TrkA to the cell’s surface for pain signaling.
The researchers also uncovered a critical protein, G Alpha Interacting Protein C-terminus 1 (GIPC1), that links TrkA and NRP1, facilitating the transport of the pain signaling complex into the cell’s interior. This newfound understanding of the pain signaling complex opens up avenues for developing novel treatments that target NRP1 and disrupt the interactions between nerve growth factor, TrkA, and NRP1.
By blocking NRP1 with existing compounds or developing peptide-based analgesics that prevent the formation of the pain signaling complex, researchers hope to create safer and more effective therapies for chronic pain conditions. These findings represent a significant step forward in pain management research and offer hope for individuals suffering from debilitating pain conditions like arthritis.
The study, titled “Neuropilin-1 inhibition suppresses nerve-growth factor signaling and nociception in pain models,” was published in the Journal of Clinical Investigation. For more information, you can access the study through DOI: 10.1172/JCI183873. This research was conducted by the New York University Pain Research Center and provides valuable insights into the mechanisms of pain signaling and potential treatment approaches.
