Pain
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Lysophosphatidic acid (LPA) is involved in the pathophysiology of cholestatic pruritus and neuropathic pain. Slowly conducting peripheral afferent C-nerve fibers are crucial in the sensations of itch and pain. In animal studies, specialized neurons ("pruriceptors") have been described, expressing specific receptors, eg, from the Mas-related G-protein-coupled receptor family. ⋯ Lysophosphatidic acid microinjections activated a greater proportion of CMi fibers and more strongly than CM fibers; spicule application of LPA activated CM and CMi fibers to a similar extent but excited CM fibers more and CMi fibers less intensely than microinjections. In conclusion, we show for the first time in humans that LPA can cause pain as well as itch dependent on the mode of application and activates afferent human C fibers. Itch may arise from focal activation of few nerve fibers with distinct spatial contrast to unexcited surrounding afferents and a specific combination of activated fiber subclasses might contribute.
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Meta Analysis
Different routes of administration in chronic migraine prevention lead to different placebo responses: a meta-analysis.
Placebo response is a powerful determinant of health outcomes in several disorders. Meta-analysis of clinical trials in pain conditions shows that it can contribute up to 75% of the overall treatment effect. Placebo response deriving from different routes of administration is poorly understood in primary headaches' pharmacological prevention. ⋯ Administration route affects placebo responses in CM preventive treatment. Elucidating the underlying mechanisms that mediate a placebo response in migraine treatment is beneficial to clinical practice and drug development, especially when comparing drugs with different routes of administration, with the effect of application to the head being superior to the other routes in this study. In our study the placebo response accounted for approximately 75% of the therapeutic gain in the treatment of CM.
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Persistent postsurgical pain (PPSP) is a common and often disabling postoperative morbidity, but many questions remain about factors associated with PPSP. This systematic review and meta-analysis aimed to identify preoperative, intraoperative, and postoperative factors associated with PPSP after gynecological surgeries, namely, hysterectomy and cesarean section, and urological surgeries, namely, prostatectomy and donor nephrectomy. Overall, 18 gynecological surgery studies, 4 prostatectomy studies, and 2 donor nephrectomy studies met the review criteria, providing data that could be meta-analyzed. ⋯ Persistent postsurgical pain after gynecological and urological surgeries is common. This systematic review identified important factors associated with cesarean section and hysterectomy that can help identify women who are at high risk of PPSP. More high-quality studies with consistent methodology are needed to understand the factors associated with PPSP risk, particularly for surgeries such as prostatectomy and nephrectomy.
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Randomized Controlled Trial
Impact of variability in baseline pain on the placebo response in randomized, placebo-controlled, crossover trials in peripheral neuropathic pain.
Large placebo responses often negatively affect randomized controlled trials within the pain area. Understanding different possible factors that influence the placebo response is therefore important. In this retrospective analysis, we hypothesized that a large variability in baseline pain score would predict a greater placebo response and analyzed the impact of the coefficient of variation, SD, and difference between the highest and lowest numeric rating scale (NRS) score at baseline on the placebo response. ⋯ Placebo response in one trial did not predict placebo response in another trial. A large placebo response was not associated with a large treatment response. In conclusion, in this retrospective data analysis, there was no impact of baseline pain variability on the placebo response in controlled clinical trials with a crossover design in patients with peripheral neuropathic pain.
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Driving is a complex task that requires both the ability to rapidly identify potential hazards and respond appropriately to driving situations to avoid crashing. A great deal of research has sought to increase road safety by focusing on risky behaviours, very few of which have explored the effects of chronic pain (CP) on driving behaviour. This systematic review aimed to assess driving behaviour and motor vehicle crash risk in drivers with CP. ⋯ Moreover, our findings provide some evidence that CP could increase crash risk and change driving behaviour. Evidence-based recommendations for practitioners and policymakers are proposed regarding the risks of driving in individuals experiencing CP. Future research into CP in driving could benefit from having a unified evidence-based approach to determine behaviour at all levels of the driving task.