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