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Single Intrathecal Administration Of The Transcription Factor Decoy Ayx1 Prevents Acute And Chronic Pain After Incisional, Inflammatory, Or Neuropathic Injury, Julien Mamet, Michael Klukinov, Tony L. Yaksh, Shelle A. Malkmus, Samantha Williams, Scott Harris, Donald C. Manning, Bradley K. Taylor, Renee R. Donahue, Frank Porreca, Jennifer Y. Xie, Janice Oyarzo, Timothy J. Brennan, Alberto Subieta, William K. Schmidt, David C. Yeomans
Single Intrathecal Administration Of The Transcription Factor Decoy Ayx1 Prevents Acute And Chronic Pain After Incisional, Inflammatory, Or Neuropathic Injury, Julien Mamet, Michael Klukinov, Tony L. Yaksh, Shelle A. Malkmus, Samantha Williams, Scott Harris, Donald C. Manning, Bradley K. Taylor, Renee R. Donahue, Frank Porreca, Jennifer Y. Xie, Janice Oyarzo, Timothy J. Brennan, Alberto Subieta, William K. Schmidt, David C. Yeomans
Renee R. Donahue
The persistence of pain after surgery increases the recovery interval from surgery to a normal quality of life. AYX1 is a DNA-decoy drug candidate designed to prevent post-surgical pain following a single intrathecal injection. Tissue injury causes a transient activation of the transcription factor EGR1 in the dorsal root ganglia–dorsal horn network, which then triggers changes in gene expression that induce neuronal hypersensitivity. AYX1 is a potent, specific inhibitor of EGR1 activity that mimics the genomic EGR1- binding sequence. Administered in the peri-operative period, AYX1 dose dependently prevents mechanical hypersensitivity in models of acute incisional (plantar), inflammatory (CFA), and chronic …