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Pain. 2014 Feb;155(2):322-33. doi: 10.1016/j.pain.2013.10.015. Epub 2013 Oct 18.

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

Author information

1
Adynxx, Inc, San Francisco, CA, USA. Electronic address: jmamet@adynxx.com.
2
Department of Anesthesia, Stanford University, Stanford, CA, USA.
3
Department of Anesthesiology, University of California-San Diego, San Diego, CA, USA.
4
Adynxx, Inc, San Francisco, CA, USA.
5
Department of Physiology, University of Kentucky, Lexington, KY, USA.
6
Department of Pharmacology, University of Arizona, Tucson, AZ, USA.
7
University of Iowa, Department of Anesthesia, Iowa City, IA, USA.
8
NorthStar Consulting, LLC, Davis, CA, USA.

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.

KEYWORDS:

AYX1; Acute; Chronic; Oligonucleotide; Post-surgical pain; Prevention

PMID:
24145208
DOI:
10.1016/j.pain.2013.10.015
[Indexed for MEDLINE]

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