Yale University Research Hints at How Some Unforeseen Effects of NSAIDs Occur

A new study led by researchers from Yale University has revealed a process that was previously unidentified, through which certain NSAIDs impact the body.

Pain Killer

NSAIDs, including ibuprofen and aspirin, are very popular choices for the management of pain and inflammation. These drugs, however, often have unexpected and baffling effects on numerous conditions, including cancer and heart disease. This remains true even when given at like doses.

This new study, which was published in Immunity, could help explain why NSAIDs produce diverse clinical effects. The finding may also guide better use of the drugs going forward.

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

How NSAIDs work

Prior to this discovery, the belief was that the anti-inflammatory effects of this class of painkillers were exclusively through the blocking of some enzymes.

That explanation, however, did not fully explain the diverse clinical outcomes that different NSAIDs produce. According to researchers, some of these drugs appear to guard against heart disease while some others add to the problem.

Certain NSAIDs have also been associated with a drop in colorectal cancer cases. Still, the family of drugs can have varying effects on asthma.

In this study, scientists succeeded in spotting a new mechanism that certain NSAIDs use in fighting inflammation. They found that some drugs, including ibuprofen and indomethacin, activate nuclear factor erythroid 2-related factor 2 (NRF2). This protein sets off anti-inflammatory processes, among its numerous actions.

The observed mechanism may be behind some of the unexplained effects that these painkillers have, researchers thought.

NRF2 is known to have power over many genes that play a part in widely varied processes, which also include metabolism and immune response. It is also thought to play some role in fighting cellular stress as well as in aging and longevity.

Further research necessary

Eisenstein and her colleagues could not firmly state that NRF2 was to blame for the startling effects of NSAIDs. Their finding only hinted at that. There is a need for more research to better establish causation, the researchers said. The team stated that their finding still has to be confirmed in human trials before being considered for guiding more effective inflammation treatment.

Some other clinical trials are already looking into whether drugs that activate NRF2 can be more helpful for the treatment of inflammatory disorders, including certain cancers, asthma, and Alzheimer’s disease. Such research could guide more effective NSAID prescriptions in the future.

The findings could also uncover new use cases for NSAIDs, Eisenstein said.

Researchers are now exploring some dermatological effects that this family of drugs produces. These include rashes, hives, and allergies. They want to find out if NRF2 plays a part in their occurrence.