Translational Controls in Pain

Abstract

Pain is an unpleasant but essential sensation. On a cellular level, pain typically originates in sensory neurons called nociceptors. They undergo rapid increases in cap-dependent translation in response to noxious stimuli. The specificity of translational controls in nociceptors is governed by regulatory factors and mRNAs that collaborate to ensure precise temporal and spatial regulation of protein synthesis. Multiple signaling pathways bridge extracellular cues to nascent translation, including the mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and the integrated stress response (ISR). The torrent of information on both mechanisms and targets of translational controls in nociceptive circuits supports an enticing corollary. Targeted inhibition of aberrant translation in the cells responsible for the genesis of pain signals in the periphery affords a new strategy to prevent or reverse chronic pain states. We describe the implications of emerging insights into translational controls predominantly in the peripheral nervous system on the search for safer and more specific pain therapeutics.