Piezo1 in neuropathic pain: a putative mechanotransduction hub and underlying mechanisms.

Neuropathic pain (NP) is a chronic pain syndrome caused by damage or dysfunction in the nervous system. Its pathogenesis involves enhanced neuronal excitability, inflammatory responses, and neuron-glial interactions. Mechanotransduction, a critical process converting physical forces into biochemical signals, significantly contributes to the initiation and maintenance of NP. Piezo1 is a novel mechanosensitive membrane protein widely expressed in the dorsal root ganglion (DRG). It mediates membrane tension perception and regulates intracellular calcium influx, influencing neuronal excitability and the release of inflammatory mediators. This review systematically summarizes the structural characteristics, activation mechanisms, downstream signaling pathways, and functional expression of Piezo1 in the DRG. The analysis was based on 112 high-quality articles retrieved from databases including CNKI, Wanfang, and PubMed published between 2022 and 2025. Special attention is given to the molecular mechanisms by which Piezo1 mediates neuron-glia interactions, and how mechanical sensitivity and neuroinflammation collectively drive NP development. Furthermore, this review discusses the therapeutic potential of Piezo1 antagonists and gene regulation strategies, highlighting its scientific and clinical significance as a promising therapeutic target. This review provides a theoretical basis for a deeper understanding of mechanotransduction in NP, promoting the development and application of mechanism-oriented interventions centered on Piezo1.