%0 Journal Article %A Jessica K. Lerch %A Jessica K. Alexander %A Kathryn M. Madalena %A Dario Motti %A Tam Quach %A Akhil Dhamija %A Alicia Zha %A John C. Gensel %A Jeanette Webster Marketon %A Vance P. Lemmon %A John L. Bixby %A Phillip G. Popovich %T Stress Increases Peripheral Axon Growth and Regeneration through Glucocorticoid Receptor-Dependent Transcriptional Programs %D 2017 %R 10.1523/ENEURO.0246-17.2017 %J eneuro %P ENEURO.0246-17.2017 %X Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal glucocorticoid receptor (Nr3c1, aka GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (Mus musculus). In response to stress or GCs, adult DRG neurite growth increases through mechanisms involving GR-dependent gene transcription. In vivo, prior exposure to an acute systemic stress increases peripheral nerve regeneration. These data have broad clinical implications and highlight the importance of stress and GCs as novel behavioral and circulating modifiers of neuronal plasticity.Significance Statement Nerve injury-induced pain affects millions and is a co-morbidity factor for individuals living with traumatic spinal cord or peripheral nerve injuries. Pain is associated with aberrant plasticity and sprouting in the injured peripheral and central nervous systems. However, the mechanisms underlying these structural changes are not understood. Here, new data implicate stress hormones (steroids) and GR activation as a novel mechanism underlying enhanced sensory neuron plasticity in injured peripheral nerves. These data also have important implications for the development and care of nerve-injury induced pain, including the use of steroids as a treatment for inflammatory pain. %U https://www.eneuro.org/content/eneuro/early/2017/08/11/ENEURO.0246-17.2017.full.pdf