Expanding Knowledge on the Role of Neuropilin-1 in Chronic Pain: Nigel Bunnett, PhD, BSc

WATCH TIME: 3 minutes

"This study will rekindle interest in targeting this system for the treatment of chronic pain by identifying a new receptor for nerve growth factor."

Developing therapies for chronic pain is particularly challenging due to the complexity of pain as a biological and psychological experience, as well as the diverse conditions and mechanisms that underlie it. Chronic pain can stem from various sources, such as inflammation, nerve damage, or central sensitization. Each of these pain types involve distinct biological mechanisms, making it difficult to develop a “one-size-fits-all” treatment.

In recent news, a group of experts from the NYU Pain Research Center conducted a preclinical study in which they found that neuropilin-1 (NRP1), a protein expressed in neurons and other cell types, is required for signaling pain, even though it does not signal on its own. In the study, NRP1 was found to be coexpressed with TrkA in nociceptors and enhances nerve growth factor (NGF)/TrkA signaling by aiding TrkA’s transport to the plasma membrane and endosomes. Blocking or knocking down NRP1 reduced NGF-driven pain responses in mice, while overexpression amplified signaling. Molecular modeling revealed NGF binds to NRP1 with high affinity, forming a signaling complex with TrkA.

Above all, the study revealed that scaffolding protein GIPC1 links NRP1 and TrkA to motor proteins, which are essential for NGF-evoked nociceptor activation and pain. In a recent interview with NeurologyLive®, lead investigator Nigel Bunnett, PhD, BSc, provided insight on the literature behind NRP1 and how this study fills some of the current knowledge gaps. Bunnett, professor and chair of the Department of Molecular Pathobiology at NYU College of Dentistry, spoke about the potential of NRP1 as a therapeutic target, as well as the next steps in expanding this research. Furthermore, he talked about structural analysis and molecule design to block the NGF-NRP1 complex, offering new avenues for addressing pain across a range of disorders.

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