Abstract
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 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.
Original language | English (US) |
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Pages (from-to) | 322-333 |
Number of pages | 12 |
Journal | Pain |
Volume | 155 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2014 |
Bibliographical note
Funding Information:The authors thank Dr. Brenda Bart-Knauer (U.S. Army Medical Research & Material Command Telemedicine & Advanced Technologies Research Center (TATRC) for her great support and guidance in the accomplishment of this work . This study was funded by Adynxx, Inc. and supported by a US Army/TATRC Grant (award no. W81XWH-10-2-0012 ).
Keywords
- AYX1
- Acute
- Chronic
- Oligonucleotide
- Post-surgical pain
- Prevention