title: Opioids Inhibit Angiogenesis in a Chorioallantoic Membrane Model.
abstract: Angiogenesis is an important characteristic of cancer. Switching from the avascular phase to the vascular phase is a necessary process for tumor growth. Therefore, research in cancer treatment has focused on angiogenesis as a drug target. Despite the widespread use of opioids to treat pain in patients with cancer, little is known about the effect of these drugs on vascular endothelium and angiogenesis.
  
  
  
  We aimed to investigate the efficacies of morphine, codeine, and tramadol in 3 different concentrations on angiogenesis in hens' eggs.
  
  
  
  This is a prospective, observational, controlled, in-vivo animal study.
  
  
  
  Single academic medical center.
  
  
  
  This study was conducted on the chorioallantoic membrane (CAM) of fertilized hens' eggs. The efficacies of morphine, codeine, and tramadol in 3 different concentrations were evaluated on angiogenesis in a total of 165 hens' eggs.
  
  
  
  Statistically significant differences were found between drug-free agarose used as a negative control and concentrations of morphine of 10 µM and 1 µM, a concentration of tramadol of 10 µM, and concentrations of codeine of 10 µM and 1 µM. Concentrations of morphine of 10 µM and 1 µM showed strong antiangiogenic effects. While codeine had strong antiangiogenic effects at high concentrations, at 0.1 µM it was shown to have weak antiangiogenic effects. However, tramadol at a concentration of 10 µM had only weak antiangiogenic effects.
  
  
  
  This is just a CAM model study.
  
  
  
  In this study, we tested the effects of 3 different opioid drugs on angiogenesis in 3 different concentrations, and we observed that morphine was a good anti-angiogenic agent, but tramadol and codeine only had anti-angiogenic effects at high doses.Key Words: Morphine, codeine, tramadol, opioid, bevacizumab, chorioallantoic membrane (CAM), angiogenesis.
authors.affiliation: Dept. of Pain Management Center, Dicle University.
authors.forename: Haktan
authors.initials: H
authors.lastname: Karaman
authors.affiliation: Dept. of Anesthesiology, Dicle University.
authors.forename: Adnan
authors.initials: A
authors.lastname: Tufek
authors.affiliation: Dept of Histology and Embryology, Dicle University.
authors.forename: Evren
authors.initials: E
authors.lastname: Karaman
authors.affiliation: Dept. of Anesthesiology, Dicle University.
authors.forename: Orhan
authors.initials: O
authors.lastname: Tokgoz
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply*; D003061:Codeine / Q000494:pharmacology; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011446:Prospective Studies; D014147:Tramadol / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol; D003061:Codeine