Neuroimmune mechanisms of lipocalin 2 in mediating chronic pain and itch

Lipocalin 2 (LCN2), a member of the lipocalin superfamily, is expressed and secreted by various cells and functions as a transport protein for lipophilic small molecules such as steroids, lipopolysaccharides, iron and fatty acids. LCN2 plays a significant role in pain modulation, particularly in the development and maintenance of inflammatory pain and chronic neuropathic pain. Its mechanisms involve the regulation of neuroinflammation and the modulation of neuron-glia interactions. LCN2 also demonstrates notable effects in itch regulation, where it binds to specific receptors and activates downstream signaling pathways, contributing to the induction and persistence of chronic itch. This review summarizes recent advances in the fundamental research on LCN2 in the regulation of chronic pain and itch, and discusses its potential value as a therapeutic target, aiming to provide a theoretical foundation for developing novel treatment strategies.