ABSTRACT
Currently available drugs for the treatment of pain, including the treatment of acute or nociceptive pain as well as for persistent or neuropathic pain, are clearly efficacious, but their clinical usefulness is limited by a variety of side effects. Often, the first line of therapy, particularly for mild to moderate pain, is aspirin and related nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen (paracetamol). For moderate to severe pain, NSAIDs still are the drugs of choice in most regions of the world, whereas opioid agonists and mixed agonist-antagonists are also used in the United States. Each of these classes of drugs has the potential to produce highly undesirable side effects. The currently available NSAIDs, which inhibit both cyclooxygenase 1 and 2 (COX 1 and 2) can produce gastrointestinal lesions and potentially fatal bleeding if used long enough at sufficiently high doses. Newer NSAIDs that selectively inhibit COX-2 may avoid the gastrointestinal lesions of the older compounds. However, there appears to be a ceiling to the maximal pain relief that can be achieved with NSAIDs, including, and perhaps particularly, COX-2 inhibitors. Opioids are effective in relieving even severe pain, but the use of opioids is markedly constrained throughout the world because of their abuse liability and potential to produce physical dependence after repeated administration. Even with brief administration, opioids produce side effects such as constipation, respiratory depression, and changes in sensorium, which can be quite problematic and place limitations on their clinical use. Additional pharmacological approaches for the treatment of pain are clearly needed.
