Soluble Nanomedicine Against Soluble Neurosensitizers to Effectively Relieve Osteoarthritis Pain and Joint Damage

ABSTRACT Targeting soluble neurosensitizers in the osteoarthritis (OA) joint cavity is a key strategy for alleviating OA pain. Soluble neurosensitizers are ubiquitous in the joint cavity and cause uncontrollable growth and sensitization of nociceptor axons therein. However, eliminating these soluble nerve growth factors (NGFs) remains a considerable challenge due to the diversity of neurosensitizers and the complexity of OA pathology. This study introduces an innovative soluble nanodrug (LAC)‐based strategy to eliminate three key neurosensitizers (H + , NGF, and netrin‐1) to simultaneously relieve OA‐associated pain and joint damage. In two animal model experiments, LAC significantly reduced pain and alleviated OA progression by reducing synovial inflammation and inhibiting cartilage and subchondral bone damage. This strategy of using soluble nanomedicine to counter soluble neurosensitizers not only provides inspiration for eliminating pain, but also sheds light on possible solutions for advancing OA treatment strategies.