The Neurological Safety of an Epidurally Administered Lipo-PGE1 Agonist in Rats

Reg Anesth Pain Med. 2017 Jan/Feb;42(1):75-81. doi: 10.1097/AAP.0000000000000520.

Abstract

Background and objective: Liposomal prostaglandin E1 (Lipo-PGE1) can inhibit platelet aggregation and vasodilatation and has been found to be therapeutic in ischemia and spinal diseases including stenosis. However, the neurologic safety of epidural administration of lipo-PGE1 requires further study. We investigated the neurotoxicity of epidurally administered lipo-PGE1 agonist in rats.

Methods: Twenty-seven rats were randomly divided into three groups: Epidural isotonic sodium chloride solution administration (negative control, group N, n = 9); epidural lipo-PGE1 agonist (group L, n = 9); and epidural alcohol (positive control, group A, n = 9). A single 3-mL injection of lipo-PGE1 agonist (0.3 mL, 0.15 μg/kg), 40% ethanol, or isotonic sodium chloride solution was administered. Neurologic assessments were performed 3, 7, and 21 days after the injection. Histopathologic data were evaluated by one pathologist via light microscopy.

Results: All rats in groups N and L, except one rat in group L, demonstrated normal response to neurologic assessments. Histopathologic findings showed no evidence of degenerative myelopathy, chromatolysis, or myelin loss in group N or L at any time point. However, all rats in group A revealed sensory and motor deficits as well as histopathologic abnormalities.

Conclusion: Liposomal prostaglandin E1 agonist did not cause any apparent neurologic abnormalities in the spinal cord or dorsal root ganglion, suggesting it is neurologically safe for epidural injection in this species. Additional mammalian study is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alprostadil / administration & dosage*
  • Alprostadil / adverse effects
  • Alprostadil / agonists*
  • Animals
  • Epidural Space / drug effects*
  • Epidural Space / pathology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / pathology
  • Injections, Epidural / methods
  • Liposomes
  • Male
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Liposomes
  • Alprostadil