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A Neurite Outgrowth Assay and Neurotoxicity Assessment with Human Neural Progenitor Cell-Derived Neurons
Published on: August 6, 2020
Cytotoxicity of Oxycodone and Morphine in Human Neuroblastoma and Mouse Motoneuronal Cells: A Comparative Approach
Merja Kokki1,2, Maija Pesonen3, Piia Vehviläinen4
1Anaesthesiology and Intensive Care Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
Background And Objectives:
Oxycodone is the mo st commonly used opioid for the treatment of moderate to severe pain. The peak cerebrospinal fluid concentration after epidural oxycodone was reported to be 300-fold greater (0.025 mM) than when administered intravenously after gynecologic surgery. Additionally, those patients administered epidural oxycodone had lower pain scores, needed less rescue analgesics and had fewer adverse effects compared with intravenous administration. However, oxycodone neurotoxicity requires evaluation before intrathecal implementation for routine clinical use.
Methods:
We used two in vitro cell culture models to compare the cytotoxicity of oxycodone with that of morphine, and to study the mechanisms underlying toxicity. Human neuroblastoma cells and mouse motoneuronal cells were treated with increasing concentrations (0.0125-2 mM) of oxycodone or morphine, and were harvested at 24, 48 or 96 h. Cell cultures were evaluated with 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide and resazurin reduction assays.
Results:
Both morphine and oxycodone decreased cell viability in a dose-dependent manner at concentrations between 0.5 and 2 mM. Morphine increased the number of apoptotic cells compared with oxycodone when assessed by flow cytometry, and transmission electron microscopy images revealed that exposure to both opioids evoked the appearance of numerous electron-dense, probable autophagic vacuoles in the cytoplasm of the cells.
Conclusions:
Based on these results, it seems that the cytotoxicity of oxycodone in motoneuronal cells is similar to or less than that of morphine, and occurs only at concentrations above the peak clinical concentration in the cerebrospinal fluid after epidural administration.
Insights
Oxycodone shows similar or lower neurotoxicity than morphine in cell cultures. Its cytotoxicity occurs only at concentrations higher than those found in cerebrospinal fluid after epidural administration.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Oxycodone is a common opioid for moderate to severe pain.
- Epidural oxycodone leads to higher cerebrospinal fluid concentrations and fewer adverse effects than intravenous administration.
- The neurotoxicity of oxycodone requires further investigation for intrathecal use.
Purpose of the Study:
- To compare the cytotoxicity of oxycodone and morphine in vitro.
- To investigate the mechanisms of opioid-induced neurotoxicity.
Main Methods:
- Utilized human neuroblastoma and mouse motoneuronal cell cultures.
- Treated cells with varying concentrations of oxycodone or morphine (0.0125-2 mM) for 24-96 hours.
- Assessed cell viability using MTT and resazurin assays; analyzed apoptosis via flow cytometry and electron microscopy.
Main Results:
- Both oxycodone and morphine reduced cell viability in a dose-dependent manner at concentrations of 0.5-2 mM.
- Morphine induced higher rates of apoptosis compared to oxycodone.
- Opioid exposure resulted in the formation of autophagic vacuoles in neuronal cells.
Conclusions:
- Oxycodone exhibits similar or less cytotoxicity than morphine in motoneuronal cells.
- Oxycodone-induced cytotoxicity is observed only at concentrations exceeding peak clinical cerebrospinal fluid levels after epidural administration.
- These findings support the potential for safe intrathecal use of oxycodone, warranting further clinical evaluation.
