Pain Relief: How NSAIDs Work

NSAIDs -- or nonsteroidal anti-inflammatory drugs -- are among the most common pain relief medicines in the world. Every day more than 30 million Americans use them to soothe headaches, sprains, arthritis symptoms, and other daily discomforts, according to the American Gastroenterological Association. And as if that wasn't enough, in addition to dulling pain NSAIDs also lower fever and reduce swelling.

But how do those little pills do so much? And if they're so good in some ways, why do they also raise the risk of heart problems in some people? The answer is complicated. Even researchers don't fully understand how NSAIDs work.

Nonetheless, with the benefits and risks of NSAIDs in the headlines frequently, ishonest turned to four experts for a rundown of what researchers do know. Our panel consisted of:

• Byron Cryer, MD, a spokesman for the American Gastroenterological Association and an associate professor of medicine at the University of Texas Southwestern Medical Center in Dallas.
• Nieca Goldberg, MD, a spokeswoman for the American Heart Association and chief of Women's Cardiac Care at Lennox Hill Hospital in New York.
• John Klippel, MD, president and CEO of the Arthritis Foundation in Atlanta.
• Scott Zashin, MD, clinical assistant professor at the University of Texas Southwestern Medical Center in Dallas and author of Arthritis Without Pain.

Here is their explanation of how NSAIDs help ease your pain -- and sometimes cause side effects in the process.

What Is Pain?

First, it helps to understand what pain is. On a basic level, pain is the result of an electrical signal being sent from your nerves to your brain.

But the process is not only electrical. When you get injured -- say with a sprain -- the damaged tissue releases chemicals called prostaglandins, which are like hormones. These prostaglandins cause the tissue to swell. They also amplify the electrical signal coming from the nerves. Basically, they increase the pain you feel.

How Do NSAIDs Help Relieve Pain?

NSAIDs work on a chemical level. They block the effects of special enzymes -- specifically Cox-1 and Cox-2 enzymes. These enzymes play a key role in making prostaglandins. By blocking the Cox enzymes, NSAIDs stop your body from making as many prostaglandins. This means less swelling and less pain.

Most NSAIDs block both Cox-1 and Cox-2 enzymes. They include the over-the- counter drugs:

• Aspirin (Bufferin, Bayer, and Excedrin)
• Ibuprofen (Advil, Motrin, Nuprin)
• Ketoprofen (Actron, Orudis)
• Naproxen (Aleve)

Other NSAIDs are available by prescription. They include:

• Daypro
• Indocin
• Lodine
• Naprosyn
• Relafen
• Vimovo
• Voltaren

Aspirin has some benefits that other NSAIDs do not. The biggest is that aspirin works against the formation of blood clots. As a result, you are less likely to form the clots that can cause heart attacks and strokes. Other NSAIDs do not have this effect.

Cox-2 inhibitors are a newer form of prescription NSAID. As you might guess, they only affect Cox-2 enzymes and not Cox-1. Two of them -- Bextra and Vioxx -- are no longer sold because of concerns about their side effects. The third, Celebrex, is still available.

What Are the Side Effects from Standard NSAIDs?

Most people who use NSAIDs don't have any serious problems with them. But in some -- especially those who need pain relief regularly -- there can be a downside.

When you swallow a pill, it affects your whole system, not just the part that hurts. So while an NSAID may do a great job of easing your pain, it may also be having other effects -- some of them unwanted -- in other parts of your body.

The most common risk of standard NSAIDs is that they can cause ulcers and other problems in your esophagus, stomach, or small intestine.

Why? NSAIDs prevent the creation of prostaglandins, the hormone-like chemicals that cause swelling and increase pain. But that's not all that prostaglandins do. There are actually many different types of prostaglandins in your body.

One type of prostaglandin helps protect the lining of the stomach and GI tract. And the Cox-1 enzyme helps make this prostaglandin. Since regular NSAIDs block Cox-1 enzymes, they slow down the manufacture of this prostaglandin. This is why standard NSAIDs cause high rates of gastrointestinal problems. With its defenses down, your GI tract becomes irritated and damaged by normal gastric acids.

How can NSAIDs affect your blood pressure? NSAIDs reduce the blood flow to the kidneys, which makes them work more slowly. When your kidneys are not working well, fluid builds up in your body. The more fluid in your bloodstream, the higher your blood pressure. It's that simple.

If you take NSAIDs in high doses, the reduced blood flow can permanently damage your kidneys. It can eventually lead to kidney failure and require dialysis.

NSAIDs can also cause extreme allergic reactions, especially in people with asthma. Experts aren't sure why. Many specialists recommend that people who have asthma stay away from any NSAID, especially if they have sinus problems or nasal polyps.

How Are Cox-2 inhibitors Like Celebrex Different?

Cox-2 Inhibitors are a type of NSAID, and generally they work in similar ways. They are no better or worse at relieving pain. They have most of the same risks.

But there is a vital difference. Cox-2 inhibitors were specifically designed to avoid the gastrointestinal problems common to other NSAIDs.

Most NSAIDs affect levels of both Cox-1 and Cox-2 enzymes. Cox-2 inhibitors only block the Cox-2 enzyme. So these drugs don't affect the prostaglandins that protect the lining of your GI tract. Cox-2 inhibitors offer the same pain relief as standard NSAIDs, but a much lower risk of gastrointestinal problems.

What Are the Risks of Cox-2 Inhibitors?

In a normal body, the levels of Cox-1 and Cox-2 enzymes are naturally in balance. When you block one but not the other, unexpected things can happen.

It turns out that the Cox-1 enzymes also help make a chemical that encourages blood clotting and tightens the arteries. Normally, these nasty effects are kept in check by another chemical called prostacyclin. But prostacyclin is made, in part, with the help of Cox-2 enzymes -- the enzymes that drugs like Celebrex block.

Blocking only Cox-2 upsets the balance of these enzymes. Levels of prostacyclin go down, the influence of Cox-1 goes unchecked, and your risk of heart attacks and strokes goes up.

This is why Cox-2 inhibitors have been linked to an increased risk of heart attacks and strokes. The dangers were considered so high for the drug Vioxx that it was taken off the market. Bextra, another Cox-2 inhibitor, was also removed from the market partly because of the same risk.

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