ASIC pH-sensitive ion channels and inflammatory pain

Tissue acidosis accompanies painful inflammatory and ischaemic conditions, edema, and fracture. It is directly linked to pain perception by opening of proton-gated cation channels present on sensory neurons. These acid-sensing ion channels (ASIC) are able to trigger action potentials on nociceptors under small changes of extracellular pH. Different ASIC isoforms have been cloned and they form functionnal channels as homo- and hetero-tetramers. Their gene expression increases during inflammation suggesting that these ion channels may take part in the hypersensitivity observed in the inflamed area. Administration of non-steroidal antiinflammatory drugs (NSAIDs) reduces low-pH induced pain. Such compounds (like acetyl-salicylic acid, diclofenac, and ibuprofen) act concomitantly on prostaglandin synthesis through inhibition of cyclooxygenases and on ASIC. This latter action is direct by blocking ASIC current and could contribute to topical antalgic affect of NSAIDs in different inflammatory states.