Changes in gene expression are required for neuronal plasticity that drives chronic pain. Immune cells respond to injury through the release of cytokines, chemokines and growth factors that then induce pathological neuronal plasticity in the excitability of nociceptors, the primary pain-sensing neurons innervating the entire body. Work in the laboratory of the scientific founders of 4E Therapeutics demonstrates that these immune-derived factors change gene expression at the level of translation. Our hypothesis is that the final common pathway linking injury to nociceptor plasticity driving chronic pain is MNK-mediated phosphorylation of eIF4E. This signaling causes translation of a distinct subset of mRNAs that cause nociceptors to become hyperexcitable. Our goal is to target MNK with novel inhibitors to alleviate the most difficult to treat chronic pain disorders, such as neuropathic pain.