COX-2-Selective Inhibition: A New Advance in Pain Management
Pain is one of the most common symptoms of tissue injury and disease and, although a necessary protective mechanism in many situations, if left untreated can persist even after the underlying tissue damage has healed. Despite our best efforts, many surgical patients receive inadequate pain relief, not only partly due to the limitations of current therapeutic options, but also due to inadequate assessment techniques and insufficient information on drug tolerance. Therefore, an important goal for the future will be to maximize pain management services by optimizing the use of current assessment techniques and therapeutic drugs, and by adopting new assessment and therapeutic technology to provide the best possible treatment for patients. This supplement begins by discussing in detail the current approaches to pain management, the unmet needs and undermanagement of pain, the future goals for the improvement of pain services, and the potential clinical and fiscal benefits. In recent years, cyclo-oxygenase (COX)-2-selective inhibitors have provided therapeutic options when treating chronic pain and inflammation. This supplement introduces a novel, injectable COX-2-selective inhibitor, parecoxib sodium, and discusses its potential uses in the management of acute pain.
Understanding how pain is undermanaged is key to the improvement of patient pain relief, comfort and mobilization. Clearly, the improper assessment of postoperative pain is one factor in the undermanagement of acute pain. Recent guidelines published in the USA by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) stated that patients have the right to appropriate assessment and the management of pain. These guidelines also recommended that pain be treated as the fifth vital sign, i.e. that patients should be assessed for pain every time their core temperature, blood pressure, pulse and respiration are measured . Healthcare services from many countries in Europe already have guidelines for the management of acute pain. The implementation of such guidelines in clinical practice should allow us to begin fulfilling our goal for the future and provide effective pain management for all patients through appropriate assessment techniques, increased patient education and awareness about their pain management, and the development of novel therapeutic approaches.
In addition to changing our approach to the assessment of pain, exploring new treatment approaches is vital for the improvement of acute pain management. Current therapeutic strategies for the management of acute pain are largely dependent on opioid analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Alternatives include combinations of analgesic products, local anaesthetics, and nerve and neuraxial blocks. Opioids, although highly effective in managing pain, have a range of side-effects such as respiratory depression, central nervous system (CNS) depression/sedation, nausea and vomiting . Neuraxial and nerve blocks can provide effective analgesia. However, tachyphylaxis, which is a side-effect of such treatment, can limit use of this technology . Multimodal therapy is recommended in postoperative surgical patients to reduce their opioid consumption by co-administering non-opioid analgesics such as NSAIDs . The opioid-sparing effect of NSAIDs is clinically relevant, as it may improve pain relief while reducing opioid-related side-effects. However, perioperative use of NSAIDs is also associated with a range of adverse effects that limit their application in a surgical setting.
Conventional non-specific cyclo-oxygenase (COX) inhibitors, such as NSAIDs, have considerable efficacy in the management of pain and inflammation associated with arthritis and other painful conditions, including postsurgical pain . However, because of non-selective COX-1 enzyme inhibition, these drugs are associated with significant incidences of mortality and morbidity . Inhibition of platelet function and a risk of increased gastrointestinal ulceration and bleeding are the most frequent complications. Disruption of platelet function by conventional NSAIDs can lead to inhibition of platelet aggregation and prolonged bleeding times, which may be a particular concern if prescribing these agents for the management of surgical pain. Furthermore, bleeding risks associated with conventional NSAIDs can complicate gastrointestinal ulceration and perforation, resulting in haemorrhagic upper gastrointestinal ulcers that can be potentially life threatening . An understandable fear of these side-effects denies this therapeutic approach to many patients in pain.
Highly selective COX-2 inhibitors (celecoxib and rofecoxib) are now available for the treatment of rheumatoid arthritis and osteoarthritis, and they are effective when treating inflammation and pain [7,8]. Clinical studies have confirmed the predicted improved safety profile of COX-2-selective inhibitors, especially with respect to gastrointestinal ulceration and bleeding. Unlike conventional NSAIDs, celecoxib has limited effects on platelet aggregation and bleeding times, and the incidence of new gastrointestinal ulceration during treatment is similar to that of placebo.
There is a need for an injectable COX-2-selective inhibitor for the management of acute pain that, in contrast to conventional anti-inflammatory agents such as ketorolac, is devoid of effects on the gastro-intestinal mucosa and on platelet function. Parecoxib sodium is a water-soluble prodrug of valdecoxib - a novel, potent COX-2-selective inhibitor. Both drugs are undergoing clinical trials for the treatment of acute pain and inflammation. The data indicate that parecoxib sodium provides rapid onset of analgesia, which is comparable with conventional NSAIDs in treating postsurgical pain. Additionally, parecoxib sodium has a significantly improved safety profile, particularly with respect to platelet safety and gastrointestinal complications. Current data on this promising new development will be reviewed.
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