Yale study explains new mode of action of painkillers

May 25, 2022
Yale study explains new mode of action of painkillers

Researchers at the Yale School of Medicine have uncovered another unknown effect of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, which are typically used to treat pain and inflammation. The new mechanism of action was exposed through laboratory experiments of cell cultures and mice.

It is generally understood that NSAIDs act through the inhibition of certain enzymes, however, this mechanism does not account for its varying clinical outcomes. For example, some NSAIDs prevent heart disease while others cause it, some NSAIDs have been linked to decreased incidence of colorectal cancer, and various NSAIDs can have a wide range of effects on asthma.

“It’s interesting and exciting that NSAIDs have a different mode of action than what was known previously,” said Anna Eisenstein, an instructor at the Yale School of Medicine. “And because people use NSAIDs so frequently, it’s important we know what they’re doing in the body [and] these findings are suggestive of that.”

The researchers discovered that some NSAIDs – including indomethacin, which is used to treat arthritis and gout, and ibuprofen – also activate a protein called nuclear factor erythroid 2-related factor 2 (NRF2). Among its many responsibilities, NRF2 controls a large number of genes involved in important processes, including metabolism, immune response, and inflammation. The protein has been implicated in aging, longevity, and cellular stress reduction as well.

This research could inform several clinical trials which are evaluating whether NRF2-activating drugs are effective in treating inflammatory diseases like Alzheimer’s disease, asthma, and various cancers. Eisenstein additionally hints at new applications for NRF2-activating NSAIDs and non-NRF2-activating NSAIDs – the drugs might be more effectively prescribed going forward.

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Category: Education, Features

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