• Pain · Feb 2014

    Single intrathecal administration of the transcription factor decoy AYX1 prevents acute and chronic pain following incisional, inflammatory or neuropathic injuries.

    • 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, and David C Yeomans.
    • Adynxx, Inc, San Francisco, CA, USA. Electronic address: jmamet@adynxx.com.
    • Pain. 2014 Feb 1;155(2):322-33.

    AbstractThe 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 neuropathic pain (SNI) in rats. Furthermore, in a knee surgery model evaluating functional measures of postoperative pain, AYX1 improved weight-bearing incapacitance and spontaneous rearing compared to control. These data illustrate the potential clinical therapeutic benefits of AYX1 for preventing the transition of acute to chronic post-surgical pain.Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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