The Piezo (Piezoelectric) ion channels are an important class of mechanosensitive cation channels that are widely distributed across various tissues and serve as crucial mediators in the conversion of mechanical stimuli into electrical signals. The major subtypes include Piezo1 and Piezo2: Piezo1 is primarily expressed in endothelial cells and certain sensory neurons, playing a role in the modulation of mechanical pain, whereas Piezo2 is predominantly localized in the dorsal root ganglia where it is essential for the transmission of touch and pain sensations. Emerging studies have demonstrated that Piezo channels are critically involved in the onset and maintenance of cancer pain, inflammatory pain, and neuropathic pain. This review summarizes recent advances in the research on mechanosensitive Piezo ion channels and their signaling pathways in various pain types, providing potential therapeutic targets and theoretical foundations for the development of novel analgesic strategies.