Pain
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Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and meta-analysis of preclinical studies of the commercially successful drug pregabalin. Our primary objective was to describe design characteristics and outcomes of studies testing the efficacy of pregabalin in behavioral models of pain. ⋯ However, we were unable to show any clear relationships between preclinical design characteristics and effect sizes. Our findings suggest opportunities for improving the design and reporting of preclinical studies in pain. They also suggest that factors other than those explored in this study may be more important for explaining the discordance between outcomes in animal models of pain and those in clinical trials.
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Epidemiological and cross-sectional studies have shown that post-traumatic stress disorder symptoms (PTSS) are common and impairing in youth with chronic pain. Yet, the co-occurrence of PTSS and pediatric chronic pain has not been examined longitudinally, which has limited understanding of theoretically proposed mechanisms (eg, sleep disturbance) underlying the PTSS-pain relationship over time. This longitudinal study aimed to fill this gap. ⋯ Higher levels of baseline PTSS were predictive of increases in pain interference at follow-up. Furthermore, subjective sleep disturbances mediated the relationship between baseline PTSS and follow-up pain interference. These findings lend support to conceptual models of PTSS-pain co-occurrence and highlight a critical need to assess and address trauma and sleep disturbances in youth with chronic pain.
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Selective targeting of sodium channel subtypes Nav1.7, Nav1.8, and Nav1.9, preferentially expressed by peripheral nociceptors, represents a unique opportunity to develop analgesics devoid of central side effects. Several compounds that target Nav1.7 and Nav1.8 with different degrees of selectivity have been developed and are currently being tested in clinical trials for multiple pain indications. Among these chemicals, benzothiazole-like compounds emerged as potent sodium channel blockers. ⋯ Pain reduction in mice occurs at doses consistent with those adopted in clinical trials. The present findings confirm the relevance of selective targeting of peripheral Nav1.8 channels to pain therapy. In light of the excellent tolerability of dexpramipexole in humans, our results support its translational potential for treatment of pain.
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Opioids are the recommended form of analgesia for patients with persistent cancer pain, and regular dosing "by the clock" is advocated in many international guidelines on cancer pain management. The development of sustained-release opioid preparations has made regular dosing easier for patients. However, patients report that the intensity and impact of their cancer pain varies considerably day to day, and many try to find a trade-off between acceptable pain control and impact of cognitive (and other) adverse effects on daily activities. ⋯ We found no clear evidence demonstrating superiority of regular dosing of opioids compared with as-needed dosing in persistent cancer pain, and regular dosing was associated with significantly higher total opioid doses. There was, however, a paucity of trials directly answering this question, and low-quality evidence limits the conclusions that can be drawn. It is clear that further high-quality clinical trials are needed to answer this question and to guide clinical practice.
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International clinical practice guidelines for low back pain (LBP) contain consistent recommendations including universal provision of information and advice to remain active, discouraging routine referral for imaging, and limited prescription of opioids. This systematic review describes usual care provided by first-contact physicians to patients with LBP. Studies that reported the assessments and care provided to people with LBP in family practice and emergency departments (EDs) from January 2000 to May 2019 were identified by searches of PubMed, EMBASE, and CINAHL. ⋯ Large numbers of patients who saw a physician for LBP received care that is inconsistent with evidence-based clinical practice guidelines. Usual care included overuse of imaging and opioid prescription and underuse of advice and information. Suboptimal care may contribute to the massive burden of the condition worldwide.