Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common types of drugs used to treat pain and inflammation. The most common NSAIDs include ibuprofen and aspirin.
However, these drugs tend to affect people in many different (often unexpected) ways, even if given at similar doses. They can also impact diseases like heart disease and cancer. Up until now, the underlying mechanism causing these disparate responses to NSAIDs has been little understood. Generally, NSAID’s mechanism of action has long been believed to focus on preventing the activity of certain enzymes in the body. However, the range of responses to NSAIDs (e.g., some NSAIDs can improve or prevent heart disease while others can cause it or make it worse) aren’t always explained by this enzyme inhibition mechanism.
A new study conducted by researchers at Yale University may have uncovered some clues.
Published in Immunity, researchers have developed a better understanding about why certain NSAIDs produce varying responses, informing how these vital drugs could be used more effectively for pain and inflammation management in the future.
To better understand NSAIDs' myriad effects, researchers used mice studies to uncover answers. They found something rather interesting. Certain NSAIDs (such as indomethacin and ibuprofen) activate a specific protein that initiates anti-inflammation pathways in the body: nuclear factor erythroid 2-related factor 2 (NRF2).
This finding essentially provides evidence that how we thought NSAIDs worked isn’t always true in all cases. Though there isn’t enough evidence yet to say conclusively that the differing effects people experience when taking NSAIDs are the direct result of NRF2, the findings from this preliminary study suggest there is a connection warranting more research.
The next step is to examine the connection between NSAIDs and NRF2 in humans and better understand these anti-inflammatory processes. Ultimately, if NRF2 activation is an underlying reason for differing responses to NSAIDs, this is crucial to the effective prescription of these drugs in the future. Understanding which NSAIDs trigger NRF2 activation and which don’t can help doctors suggest these medications for certain conditions with more accuracy.