Translational control of chronic pain

Pain is a crucial physiological response to injury and pathologies. The development and maintenance of pain requires the expression of novel genes. The expression of such genes occurs in highly regulated and orchestrated manner where protein translation provides an exquisite temporal and spatial fidelity within the axons and dendrites of neurons. Signaling pathways that regulate local translation are activated by cytokines, neurotrophic factors, or neurotransmitters, which are released either due to tissue damage or neuronal activity. In recent years, the ERK and mTOR pathways have been demonstrated to be central in regulating local translation in neurons of both the peripheral and central nervous systems in diverse models of chronic pain. The ERK and mTOR pathways converge onto the cap-dependent translational machinery that regulates genes essential for the development of nociceptive sensitization. Moreover, inhibition of these pathways has proved to be effective in normalizing the biochemical changes and the associated pain in various preclinical models.