Posttranslational mechanisms of peripheral sensitization

The sensation of pain can be dramatically altered in response to injury or disease. This sensitization can occur at the level of the primary sensory neuron, and can be mediated by multiple biochemical mechanisms, including, but not limited to, changes in gene transcription, changes in translation, stability, or subcellular localization of translated proteins, and post-translational modifications. This review focuses on post-translational modifications to ion channels expressed in primary sensory neurons that form the machinery driving peripheral sensitization and pain hypersensitivity. Studies published to date show strong evidence for modulation of ion channels involved in transduction and transmission of nociceptive inputs coincident with biophysical and behavioral sensitization. The roles of phosphorylation and oxidation/reduction reactions of voltage-dependent sodium, potassium, and calcium channels are discussed, as well as phosphorylation-mediated modulation of sensory transduction channels. (C) 2004 Wily Periodicals, Inc.