Acid-sensing ion channels and pain: therapeutic potential?

Many painful inflammatory and ischemic conditions such as rheumatoid arthritis, cardiac ischemia and exhausted skeletal muscles are accompanied by local tissue acidosis. In such acidotic states, extracellular protons provoke the pain by opening excitatory cation channels in nociceptors. From recent molecular investigations into sensory neurons, two important candidate genes (or gene families) encoding proton-activated cation channels - acid-sensing ion channel and transient receptor potential vanilloid receptor subtype-1 have emerged. Since both channels can be major pharmacological targets for pain therapy and therefore, for the development and screening of new analgesics, it is of great importance to confirm their involvement in acid-evoked pain in humans and to know their relative contribution to the nociception. The authors' recent psychophysical studies focused on these points and the data is presented and discussed in this review.