Mechanism of capsaicin receptor TRPV1-mediated toxicity in pain-sensing neurons focusing on the effects of Na+/Ca2Â + fluxes and the Ca2Â +-binding protein calretinin

► Influx of Ca2 + and Na+ via TRPV1 causes cell swelling and membrane bleb formation. ► Elevation of [Ca2 +]i sensitizes/activates TRPV1 channels augmenting cell swelling. ► Calretinin expression diminishes capsaicin-induced cell volume increases. ► Acute capsaicin toxicity results from impaired cell membrane integrity, not apoptosis.