The Anatomy of Pain

Discover the long-term side effects of NSAIDs.


| July/ August 2017


We all know what pain feels like, but few of us know the biology behind the “ouch” factor. Pain is a result of inflammation. When we are injured, the body responds with cyclooxygenase-2 or COX-2, a relatively recently discovered enzyme related to COX-1. While COX-1 enzymes are responsible for maintaining balance in the stomach and kidneys, COX-2 involves turning a stored fat called arachidonic acid into prostaglandins, which inflame injured areas and lead to pain.

Enter nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen or naproxen, over-the-counter remedies that work by inhibiting COX-1 and COX-2 enzymes. Although NSAIDs are the most popular pain-relief medications, long-term use can result in gastrointestinal upset, peptic ulcers and intestinal bleeding, and may even contribute to colon, kidney or liver damage. In fact, a report in The American Journal of Medicine revealed that more than 107,000 people are hospitalized each year due to complications from NSAID use.

In an effort to soothe pain without leaving users vulnerable to these side effects, researchers created a new generation of COX-2 inhibitors. Sold under the names Celebrex and Vioxx, these drugs also relieve pain and inflammation, but because they only target the COX-2 enzyme, they carry fewer gastrointestinal risks than traditional NSAIDs. Better yet, studies found that Celebrex was just as effective at stopping pain as narcotics without the risk of addiction, and Vioxx could conquer the toughest menstrual cramps. But while these drugs were being hailed as the new “safe” aspirin, reports began to surface of side effects, including diarrhea, headaches, respiratory infections, dizziness and skin rashes. Researchers from the University of California at Irvine found that these new pain relievers could worsen colitis and interfere with the healing of gastric ulcers. Of greater concern, the U.S. Food and Drug Administration received reports of 10 deaths within months of the release of Celebrex. Vioxx was removed from the market in 2004. Celebrex remains a popular arthritis drug.

A widely reported, large-scale study published in the New England Journal of Medicine in 2016 compared celecoxib (Celebrex), ibuprofen and naproxen, and found that Celebrex was safer than both ibuprofen and naproxen when used long-term — although some experts cite study weaknesses including a low inclusion of patients with heart disease (the most worrisome) and a high patient drop-out rate, making data interpretation difficult. Of the study, Dr. Elliott Antman, a professor of medicine at Harvard Medical School and a past president of the American Heart Association, said he would continue to advise that any of the drugs in the study be taken only by the lowest-risk patients and in the lowest dose possible for the shortest time possible. Another doctor, Michael Joseph Blaha, director of clinical research for the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, says: “I would not feel comfortable saying it is perfectly safe to take celecoxib. But if you need to take a daily pill it might be safer to take this one than [ibuprofen or naproxen].

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