How do natural and therapeutic opioids work? Researchers uncover the difference in cellular activation, revealing the key to pain-relief without addiction risk.

by time news

2023-04-20 12:30:00

The human body naturally produces opioid-like substances such as endorphins, which have pain-relieving effects. In pain therapy, on the other hand, opioid-containing drugs such as morphine or fentanyl are used. Their major disadvantage: They make you dizzy, can dangerously slow down your breathing and carry a high risk of addiction. Excessive abuse causes hundreds of thousands of deaths worldwide every year, and there has been talk of an opioid crisis in the USA for years.

Researchers at the University of Geneva (UNIGE) have investigated how natural and therapeutically used opioids work at the cellular level. In general, the substances bind to opioid receptors, which mediate a variety of physiological functions. Opioids activate these receptors, triggering a series of biochemical reactions that can reduce pain and induce euphoria. In their in »Science Advances« show that therapeutic opioids enter the interior of cells and activate opioid receptors there, while natural opioids cannot enter the cells and only activate receptors on the cell surface. The location of the activated receptors could explain why opioid drugs elicit different physiological responses than natural opioids.

The researchers used new molecular tools to study the opioid receptors with unprecedented spatial resolution. “Instead of observing changes in cells as a whole, we were able to see in detail what is happening at different locations within the cells,” explain Arthur Radoux and Lucie Oberhauser, co-authors of the study. “To do this, we developed biosensors that we could use to detect in living cells whether receptors are activated at specific locations in or on the cells and which trigger a reaction.” The scientists combined this technique with analyzes of gene expression and protein regulation. Depending on where the receptors were activated – within the cell or in the cell membrane – the triggered reaction, i.e. the signals involved in pain relief, changed.

#Painkillers #opioids #cells

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