Nonsteroidal anti-inflammatory drugs (NSAIDs) work in two ways:

• They reduce the sensation of pain.

• At higher doses, they reduce the inflammation that often accompanies and worsens pain.

NSAIDs have these effects because they reduce the production of hormone-like substances called prostaglandins. Different prostaglandins have different functions, such as making nerve cells more likely to respond to pain signals and causing blood vessels to widen (dilate).

Most NSAIDs reduce prostaglandin production by blocking both cyclooxygenase (COX) enzymes (COX-1 and COX-2), which are crucial to the formation of prostaglandins. One type of NSAID, the coxibs (COX-2 inhibitors), tend to block mainly COX-2 enzymes.

Only COX-2 enzymes are involved in the production of prostaglandins that promote inflammation and the resulting pain. These prostaglandins are released in response to an injury—burn, break, sprain, strain, or invasion by a microorganism. The result is inflammation, which is a protective response: The blood supply to the injured area increases, bringing in fluids and white blood cells to wall off the damaged tissue and remove any invading microorganisms.

Prostaglandins that are formed through the action of COX-1 enzymes help protect the digestive tract from stomach acid and play a crucial role in blood clotting. Because most NSAIDs block COX-1 enzymes and thus reduce the production of these prostaglandins, they may irritate the stomach’s lining. Such irritation can cause digestive upset, peptic ulcers, and bleeding in the digestive tract.

Because coxibs block mainly COX-2 enzymes, they are less likely to cause problems due to stomach irritation. However, coxibs block some COX-1 enzymes, so even coxibs may slightly increase the risk of these problems.