Opioid analgesics such as morphine are considered to be the most effective analgesics and are widely used to treat patients with moderate-to-severe pain. These opioid analgesics produce pain relief mainly by stimulating mu opioid receptors in the central nervous system. Advances in opioid analgesics during the past 20 years have been primarily in improved methods for the delivery of existing narcotic opioids rather than the discovery of new drugs. Patients who suffer severe pain may simultaneously receive more than one formulation of opioid analgesic and often receive other classes of analgesic medications.

Non-opioid analgesics, including acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are widely used to treat mild-to-moderate pain. NSAIDs are thought to produce analgesia by inhibiting activity of cyclooxygenase enzymes (COX-l and COX-2), thereby reducing inflammation at the site of injury or disease. Some NSAIDs require a prescription and others are available as over-the-counter medications. Recent advances in NSAID analgesia have focused primarily on reducing adverse gastrointestinal (GI) side effects.

Although morphine and other opioid analgesics are considered to be the most effective analgesics for moderate-to-severe pain, many patients who use them do not obtain complete pain relief, and they are ineffective or not well tolerated for other patients. Opioid analgesics produce a wide range of adverse effects that may include opioid bowel dysfunction, sedation, nausea, vomiting, decreased respiratory function, addiction and in some instances, death. In addition, due to their potential for abuse, most opioid analgesics are strictly regulated by the United States Drug Enforcement Agency (DEA) under the Controlled Substances Act, which imposes strict registration, record-keeping and reporting requirements, security controls and restrictions on narcotic analgesic prescriptions.

Although NSAIDs can be effective for mild-to-moderate pain, many patients are unable to tolerate NSAIDs because of GI side effects. Traditional NSAIDs produce significant adverse effects on the stomach and GI tract, including GI ulcers and bleeding. In addition, prolonged use of NSAIDs can cause liver and kidney failure.