The persistence of pain following surgery or trauma limits recovery, physical rehabilitation and the return to a normal quality of life. AYX1 is a compound developed for preventing the maintenance of post-surgical pain with a single intrathecal administration prior to surgery. Post-surgical pain arises from a combination of mechanical/incisional, inflammatory and often nerve trauma. Early in the development of pain following such injury, there are waves of gene regulation in DRG and spinal cord neurons leading to long-term sensitization and the maintenance of pain over time. These transcriptional events are necessary to the development and maintenance of pain and involve the sequential and interdependent regulation of almost all classes of encoding pain genes, including receptors, ion channels, secondary messengers, enzymes, neurotransmitters and proteasome-ubiquitin factors. One approach to alleviating pain has been to alter the expression of individual genes encoding for particular pain factors. This approach, however, is limited by robust gene plasticity and functional redundancy in the nociceptive system that overcome the sole and linear modulation of individual pain genes. The transcription factor EGR1 is a powerful molecular switch acting at the epicenter this plasticity: its activation immediately after an injury triggers the waves of gene regulation necessary for maintaining neuronal sensitization in the DRG-spinal network. AYX1 is a DNA decoy (small synthetic, dsDNA molecule) that blocks EGR1 function by mimicking the genomic sequence EGR1 normally binds. We have demonstrated that a single intrathecal delivery of AYX1 around the time of an inflammatory (CFA model), incisional (Brennan model) or neuropathic (Spared Nerve Injury model) injury in rats produces a dose-dependent prevention of ongoing tactile hypersensitivity with no evident effects upon motor function. This therapeutic profile has the potential of improving the management of acute pain following surgery and preventing the maintenance of persistent/chronic pain. This work is sponsored by Adynxx