Opioids inhibit angiogenesis in a chorioallantoic membrane model

Abstract

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.