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.