Piezo1 in Peripheral and Central Sensitisation: Implications for Chronic Pain

Piezo1 is an increasingly recognised mechanosensitive ion channel that transduces mechanical forces into electrical and biochemical signals and is expressed in peripheral sensory pathways as well as across multiple cell types within the central nervous system. Growing evidence indicates that Piezo1 contributes to nociceptive processing by influencing cellular excitability, inflammatory signalling, and neuron–glia interactions within nociceptive circuits. These actions position Piezo1 as an important contributor to amplified nociceptive transmission and circuit hyperexcitability, thereby potentially facilitating the transition from acute to chronic pain via several integrating mechanisms. In this context, Piezo1 may interact with other established mechanisms of chronic pain, including peripheral and central sensitisation and neuroinflammatory signalling, to help sustain persistent pain states. This review examines the potential roles of Piezo1 as a synergistic contributor to nociceptive hyperexcitability and considers how it may modulate nociceptive excitability, glial activation, and central sensitisation. Available findings support the view that Piezo1 participates in mechanotransduction and maladaptive plasticity relevant to chronic pain, although direct evidence for its cell-specific actions within spinal dorsal horn circuits remains limited. Piezo1 has also been implicated in tissue remodelling following spinal cord injury, suggesting that its therapeutic relevance may extend beyond pain signalling alone. Further studies will be required to clarify its mechanistic role in the mechanobiology of chronic pain and to evaluate the translational potential of targeting Piezo1 through pharmacological or genetic strategies for pain management.