Last updated: Apr 06, 2008
A third of Americans over 65 use nonsteroidal anti-inflammatory drugs (NSAIDs) every day, according to the American Pain Foundation. For the chronic pain patient, it's critical to understand the most basic drugs in your war on pain.

Most painkillers (or analgesics, from the Greek term for the absence of pain) work on the central nervous system—the brain and the spinal cord—and the peripheral nervous system, which connects the rest of the body to them, sending signals back and forth.

Painkillers are generally broken down into three categories: opioid (narcotic) analgesics, non-narcotic analgesics (which include NSAIDs), and adjuvant therapies such as anticonvulsants, muscle relaxants, and antidepressants. We'll deal with NSAIDs here.

How NSAIDs work
The granddaddy of NSAIDs is aspirin (acetylsalicylic acid), made from a compound found in willow bark and introduced into modern medicine in 1899. Ibuprofen, a non-aspirin analgesic, was introduced in 1974 and is best known as Advil or Motrin. Naproxen was first marketed in 1976, and is best known as Aleve.

Taken with care, NSAIDs are a staple of the pain patient's medicine cabinet.
Most NSAIDs work by blocking two enzymes, COX-1 and COX-2, which help produce substances that are the real villains in the pain picture, prostaglandins—hormone-like substances that perform a variety of regulatory jobs in the body.

Prostaglandins are created at the sites of injury or inflammation and cause the pain receptors in the surrounding area to become more sensitive. By decreasing prostaglandin production, NSAIDs lessen the sensation of pain and reduce inflammation.

The problem is that the COX-1 enzyme has an important job to do: It helps produce the prostaglandins that protect the stomach lining from the corrosive effects of stomach acid. When COX-1 is blocked, stomach upset, bleeding, and ulcers can occur. These are well-known side effects of all NSAIDs.

Individuals react differently to dosage, but in general, taking more than the daily recommended amount of an NSAID carries a significant risk of gastrointestinal bleeding and is unlikely to provide additional pain relief. (Parents should consult a physician before giving aspirin to a child or adolescent. When used to treat a viral infection, such as the flu or chicken pox, aspirin and other medications containing salicylates have been linked to an increased risk of developing Reye's syndrome, a potentially life-threatening illness.)

The COX-2 inhibitors
In the 1990s drugs were developed to solve the NSAIDs stomach problem. Known as COX-2 inhibitors, they primarily disable the COX-2 enzyme, leaving the COX-1 to do its job protecting the stomach. Vioxx, Celebrex, and Bextra were widely marketed, and became hugely popular prescription-only painkillers. However, in 2004 studies showed that Vioxx can increase the risk of heart attack and stroke, and its maker, Merck, yanked it from the market. More than a dozen cases went to court, and although Merck won many of them, some cases resulted in huge damages against the company. In November 2007 Merck agreed to a massive payout of $4.85 billion to settle thousands of additional cases. In 2005 Bextra was also removed. Celebrex remains on the market.

The new concerns prompted the FDA in 2005 to require new warnings on all NSAIDs (except aspirin), stating the risk of stomach, heart, or skin problems. Ulcers and gastrointestinal bleeding linked to the use of NSAIDs are responsible for an estimated 15,000 to 20,000 deaths in the U.S. each year, and more than 100,000 hospitalizations, according to the American College of Gastroenterology. In February 2007 the American Heart Association advised physicians that, except for aspirin, NSAIDs and especially COX-2 inhibitors should be used only as a last line of treatment for people with heart disease or heart disease risk factors.

All NSAIDs present an additional risk of kidney damage when used at high doses for a prolonged period of time.

The special case of acetaminophen
Acetaminophen, best known as Tylenol, isn't an NSAID. Its exact painkilling mechanism is not fully understood, and it doesn't reduce inflammation. Nor does acetaminophen have many side effects—except one whopper: It can damage the liver, sometimes fatally, if taken in large doses or by someone with liver disease (sometimes caused by long-term, regular use of alcohol).

When you calculate your daily acetaminophen or NSAID intake, watch for hidden sources. Pain patients can overdose unwittingly if they lay a dose of Tylenol, for example, over a med which combines another drug with acetaminophen, as do some opioid drugs, such as Vicodin and Percocet. Some over-the-counter remedies also bundle in acetaminophen or NSAIDs, such as Theraflu, Alka-Seltzer, and NyQuil Cold & Flu.

Taken in correct doses, however, the non-narcotic pain drugs are usually safe and can work temporary wonders.