ABSTRACT
Pain is an important warning mechanism that alerts organisms to ongoing or potential tissue damage. Ion channels are critical mediators of pain signaling pathways, and play important roles in both the initiation and the conduction of pain signals through pain sensing neurons (nociceptors). The study of ion channelopathies, along with the use of an ever-improving array of pharmacologic and toxin tools, have greatly improved our understanding of how specific channel proteins impact pain pathways. The voltage-gated channels, including sodium channels, calcium channels, potassium channels and TRP channels, are particularly important for nociceptor signaling, and pathologic pain arises when these channels are dysregulated. The role that channels play in pain has led to many attempts to modulate pain via drugs or other therapeutic interventions that impact channel density or function. Existing ion-channel-targeting drugs, like local anesthetics, are successfully used to alter pain perception in humans, but they are limited by features, like a lack of selectivity, that reduce their utility and safety. Despite the challenges, modulation of ion channels remains one of the most promising approaches for controlling pathologic pain.
