Acid-Sensing Ion Channels: A Novel Therapeutic Target for Pain and Anxiety

The acid-sensing ion channel (ASIC) has emerged as a novel type of ion channel that is activated by extracellular protons as well as nonproton ligands. Advances in ASIC research have resolved its multifaceted structural and functional properties, including its widespread distribution, polymodal activation, and activity-dependent regulation of its expression. All of these properties promote a better understanding of the roles played by pH dynamics as well as damage-related signals through activation of ASICs in pain and anxiety. Importantly, even more studies have provided strong evidence supporting the effectiveness of targeting ASICs with pharmacological agents or gene knockdown for treating pain and anxiety. Here we review the contribution of ASICs at the peripheral and central levels to the development of acute pain, inflammatory pain, neuropathic pain, and anxiety-related disorders, as well as their potential underlying mechanisms. Accumulating evidence suggests that ASICs represent a novel class of promising targets for developing effective therapies for pain and anxiety.