People usually feel pain when receptors in skin, bones, joints or other tissues are stimulated by an injury or threat to the body. Neuropathic pain is triggered by changes in the nerves themselves, or caused by changes in the brain or peripheral tissues.

Pain involves the interaction between several chemicals in the brain and spinal cord. These chemicals, called neurotransmitters, transmit nerve impulses from one nerve cell to another. Neurotransmitters stimulate receptors found on the surface of nerve and brain cells, which function like gates, allowing messages to pass from one nerve cell to the next. Many pain-relieving drugs work by acting on these receptors. For example, opioid drugs block pain by locking onto opioid receptors in the brain.

Other drugs control pain outside the brain, such as non-steroidal anti-inflammatory drugs (NSAIDs). These drugs, including aspirin, ibuprofen, and naproxen, inhibit hormones called prostaglandins, which stimulate nerves at the site of injury and cause inflammation and fever. Newer NSAIDs, including Celebrex (celecoxib) and Vioxx (rofecoxib) for rheumatoid arthritis, primarily block an enzyme called cyclooxygenase-2. Known as COX-2 inhibitors, these drugs may be less likely to cause the stomach problems associated with older NSAIDs, but their long-term effects are still being evaluated.