title: Single intrathecal administration of the transcription factor decoy AYX1 prevents acute and chronic pain after incisional, inflammatory, or neuropathic injury.
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.
authors.affiliation: Adynxx, Inc, San Francisco, CA, USA Department of Anesthesia, Stanford University, Stanford, CA, USA Department of Anesthesiology, University of California-San Diego, San Diego, CA, USA Department of Physiology, University of Kentucky, Lexington, KY, USA Department of Pharmacology, University of Arizona, Tucson, AZ, USA University of Iowa, Department of Anesthesia, Iowa City, IA, USA NorthStar Consulting, LLC, Davis, CA, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Mamet
authors.forename: Michael
authors.initials: M
authors.lastname: Klukinov
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
authors.forename: Shelle A
authors.initials: SA
authors.lastname: Malkmus
authors.forename: Samantha
authors.initials: S
authors.lastname: Williams
authors.forename: Scott
authors.initials: S
authors.lastname: Harris
authors.forename: Donald C
authors.initials: DC
authors.lastname: Manning
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Taylor
authors.forename: Renee R
authors.initials: RR
authors.lastname: Donahue
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Xie
authors.forename: Janice
authors.initials: J
authors.lastname: Oyarzo
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Brennan
authors.forename: Alberto
authors.initials: A
authors.lastname: Subieta
authors.forename: William K
authors.initials: WK
authors.lastname: Schmidt
authors.forename: David C
authors.initials: DC
authors.lastname: Yeomans
mesh_terms: D059787:Acute Pain / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D059350:Chronic Pain / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage*; D007278:Injections, Spinal; D008297:Male; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016716:PC12 Cells; D010149:Postoperative Pain / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D018836:Inflammation Mediators
keywords: AYX1; Acute; Chronic; Oligonucleotide; Post-surgical pain; Prevention