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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Pain / etiology
  • Acute Pain / pathology
  • Acute Pain / prevention & control*
  • Analgesics / administration & dosage*
  • Animals
  • Chronic Pain / etiology
  • Chronic Pain / pathology
  • Chronic Pain / prevention & control*
  • Dogs
  • Dose-Response Relationship, Drug
  • HL-60 Cells
  • Humans
  • Inflammation Mediators / administration & dosage*
  • Injections, Spinal
  • Male
  • Neuralgia / complications
  • Neuralgia / drug therapy*
  • Neuralgia / pathology
  • PC12 Cells
  • Pain, Postoperative / etiology
  • Pain, Postoperative / pathology
  • Pain, Postoperative / prevention & control*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Analgesics
  • Inflammation Mediators