Circulating Piezo 1 Levels in Complex Regional Pain Syndrome Type 1 and Their Association with Time from Neridronate...

Background: Complex Regional Pain Syndrome type 1 (CRPS-1) is a multifactorial disorder characterized by persistent pain, neuroinflammation, and tissue remodeling following trauma in the absence of overt nerve injury. Despite advances in understanding its pathophysiology, the mechanisms underlying the transition to chronic pain remain incompletely defined, and reliable circulating biomarkers are lacking. Piezo-type mechanosensitive ion channel component 1 (Piezo 1), a mechanosensitive ion channel that transduces mechanical stimuli into intracellular calcium signaling, has emerged as a regulator of inflammation, extracellular matrix remodeling, and cellular stress responses. Experimental evidence indicates that Piezo 1 activation can modulate cytokine production and mechanotransduction pathways relevant to chronic pain and inflammatory conditions. Methods: In this study, we evaluated circulating Piezo 1 levels in CRPS-1 patients and explored their association with clinical parameters and response to neridronate treatment. Results: Although Piezo 1 levels were significantly altered compared to controls, no associations were observed with pain intensity or therapeutic response. Conclusions: These findings suggest that, despite its biological relevance, circulating Piezo 1 is not a clinically informative biomarker in CRPS-1. The results support a predominantly local role of Piezo 1-mediated mechanotransduction in processes relevant to chronic inflammation and nociceptive sensitization.