1. 2017;20;SE11-SE21Opioids Inhibit Angiogenesis in a Chorioallantoic Membrane Model
   Prospective Evaluation
   Haktan Karaman, MD, Adnan Tufek, MD, Evren Karaman, MD, and Orhan Tokgoz, MD.

BACKGROUND: 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.

OBJECTIVES: We aimed to investigate the efficacies of morphine, codeine, and tramadol in 3 different concentrations on angiogenesis in hens’ eggs.

STUDY DESIGN: This is a prospective, observational, controlled, in-vivo animal study.

SETTING: Single academic medical center.

METHODS: 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.

RESULTS: 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.

LIMITATIONS: This is just a CAM model study.

CONCLUSION: 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