Reinvigorating Drug Development Around NGF Signaling for Pain

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2025 Feb 17

PMID 39959966

Authors

Andi Wangzhou

Theodore J Price

Affiliations

Soon will be listed here.

Abstract

Nerve growth factor (NGF) signaling is a clinically validated target for the treatment of several prevalent types of chronic pain; however, addressing safety concerns remain a key challenge. In this issue of the JCI, Peach et al. take a major step forward in this area by deciphering complexities in the signaling of the NGF receptor TrkA, finding that neuropilin 1 (NRP1) acted as a coreceptor for NGF actions at TrkA and the receptor complex required scaffolding from GIPC1. Using a mix of techniques, including animal behavioral models, electrophysiology on mouse and human dorsal root ganglion (DRG) neurons, and elegant biochemical pharmacology, the authors demonstrated that this therapeutic target might more safely manipulate NGF signaling to achieve pain alleviation. While there are still important questions to answer, the innovative work paves the way for the development of nonopioid pain therapeutics.

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