Pain management today - optimising the benefit/risk ratio: defining the role of weak opioids and combination analgesics.

Long-term use of both cyclooxygenase-2-specific (COX-2) inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with cardiovascular, gastrointestinal and cutaneous adverse events. In response, the European Medicines Agency (EMEA) and the United States Food and Drug Administration (FDA) reviewed the evidence and issued a series of recommendations for prescribers and consumers of these drugs. Labelling changes, including boxed warnings, were requested by FDA on all prescription NSAIDs, while the COX-2 inhibitors rofecoxib and valdecoxib were withdrawn from the market. These developments mean that anti-inflammatory drugs, the traditional first choice for pain management, should be used with caution in many patients with chronic pain requiring long-term pharmacological treatment. However, no official advice has been provided on alternative approaches to pain management in these patients. Against this background, a satellite symposium was organized at EULAR 2005 in Vienna entitled “Pain Management Today—Optimizing the Benefit/Risk Ratio: Defining the Role of Weak Opioids and Combination Analgesics” to review the evidence base for alternative, weak opioid-based analgesic regimens. This supplement to Clinical Rheumatology comprises papers developed based on the four keynote presentations at this symposium. The first article, by Professor Richard Langford, provides an overview of the issues currently facing prescribers managing patients with chronic pain. Regulatory authorities have advised caution when prescribing COX-2 inhibitors, particularly for patients at increased cardiovascular risk, and for long-term use, and have advised that nonselective NSAIDs be used at the lowest effective dose for the shortest duration. These warnings have left physicians seeking safer alternatives to anti-inflammatory drugs. In his paper, Professor Langford describes alternative analgesic strategies, focusing, in particular, on multimodal analgesia. Fixed-dose combinations outlined include paracetamol plus codeine, paracetamol plus dextropropoxyphene and paracetamol plus tramadol. He concludes that a re-evaluation of the role of weak opioids, particularly when used as part of a combination, may be the way forward in the management of chronic pain. The review by Professor Robert Raffa discusses the pharmacology that underlies these therapies, illustrating how atypical weak opioids, such as tramadol, can target pain through multiple sites of action, and that by combining two well-known analgesics, paracetamol and tramadol, synergistic analgesia can be achieved by complementary mechanisms of action. He also illuminates the pharmacological rationale behind combinational therapy that optimises onset and duration while minimising adverse events. In the third paper, Professor Stephan Schug describes clinical data on the combination of paracetamol plus tramadol. This combination has been extensively investigated in acute, subacute, and chronic pain, and as an add-on treatment to NSAIDs and COX-2 inhibitors, and has demonstrated striking efficacy and an acceptable level of side effects. The final paper reviews current guidelines on musculoskeletal pain management and presents new recommendations based on a consensus obtained at the second meeting of the Working Group on Pain Management (WGPM), an international multidisciplinary panel that was established in December 2004 to review alternatives to anti-inflammatory drugs in the management of moderate-to-severe pain. These guidelines highlight the role of paracetamol as the foundation for chronic pain management and, while acknowledging the importance of anti-inflammatory drugs in certain specific situations, strongly recommend the use of weak opioids and the combinations of paracetamol plus tramadol, in particular, in many chronic pain situations. Grunenthal is gratefully acknowledged for providing support for the symposium and the development and publication of this supplement.