Managing pain from chronic conditions, such as, but not limited to, osteoarthritis and rheumatoid arthritis, requires the clinician to balance the need for effective analgesia against safety risks associated with analgesic agents. Osteoarthritis and rheumatoid arthritis pain is incompletely understood but involves both nociceptive and non-nociceptive mechanisms, including neuropathic mechanisms. Prevailing guidelines for arthritis-related pain do not differentiate between nociceptive and non-nociceptive pain, sometimes leading to recommendations that do not fully address the nature of pain. NSAIDs are effective in treating the nociceptive arthritis-related pain. However, safety concerns of NSAIDs may cause clinicians to undertreat arthritis-related pain. In this context, combination therapy may be more appropriate to manage the different pain mechanisms involved. A panel convened in November 2010 found that among the currently recommended analgesic products for arthritis-related pain, fixed-low-dose combination products hold promise for pain control because such products allow lower doses of individual agents resulting in decreased toxicity and acceptable efficacy due to synergy between the individual drugs. Better evidence and recommendations are required to improve treatment of chronic arthritis-related pain.

Most of the effects of rhEPO occurred 48 h after dosing, when the concentration of rhEPO was less than 1% of Cmax, suggesting that the processes set in motion by rhEPO can continue after rhEPO concentrations fall. Our observation of apoptosis in erythroblasts even when rhEPO concentrations were high suggests that regulatory mechanisms which down-regulate erythropoiesis are also engaged.

Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a “do ask, do tell” approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with minimal toxicity.

Pain should be treated promptly and effectively to restore the patient to full function, avoid pain chronification, and preserve quality of life. A recent pain specialists' meeting discussed the use of different pharmacological treatment options, such as topical analgesics, nonopioid agents (such as paracetamol and nonsteroidal anti-inflammatory drugs), weak and strong opioids, and fixed-dose combination products in the management of moderate to severe pain from different etiologies. One of the topics discussed in, and subsequent to, this meeting was the role of fixed-dose combination products for nurse-prescribers who are in many ways at the front line of managing both acute and chronic pain syndromes. The panel agreed that proper product selection should take into account the patient's age, condition, type of pain, and comorbidities, as well as balance safety with effectiveness. Although nurse-prescribers need to be aware of cumulative paracetamol dosing, fixed-dose combination products, such as tramadol-paracetamol, may offer important advantages, eg, by providing opioid-sparing without sacrificing efficacy.

The family practitioner plays an important role in the prevention, diagnosis, and early management of chronic pain. He/she is generally the first to be consulted, the one most familiar with the patients and their medical history, and is likely the first to be alerted in case of inadequate pain control or safety and tolerability issues. The family practitioner should therefore be at the center of the multidisciplinary team involved in a patient's pain management. The most frequent indications associated with chronic pain in family practice are of musculoskeletal origin, and the pain is often multimechanistic. Fixed-dose combination analgesics combine compounds with different mechanisms of action; their broader analgesic spectrum and potentially synergistic analgesic efficacy and improved benefit/risk ratio might thus be useful. A pain specialist meeting held in November 2010 agreed that the fixed-dose combination tramadol/paracetamol might be a useful pharmacological option for chronic pain management in family practice. The combination is effective in a variety of pain conditions with generally good tolerability. Particularly in elderly patients, it might be considered as an alternative to conventional analgesics such as NSAIDs, which should be used rarely with caution in this population.