Pain
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Recent research has highlighted the need for a deeper understanding of the heterogeneity in trajectories of children's distress after acute pain exposure, moving beyond the group means of behavioural pain scores at a single timepoint. During preschool vaccinations, 3 distinct trajectories of postvaccination pain regulation have been elucidated, with approximately 75% of children displaying trajectories characterized by downregulation to no distress by 2 minutes postneedle and 25% concerningly failing to downregulate by 2 minutes. ⋯ Furthermore, although all children's pain-related distress at various timepoints throughout the appointment was most strongly predicted by previous pain scores, different patterns of associations emerged depending on the trajectory exhibited. This research highlights both the need to minimize distress before the needle to avoid the highly distressed trajectory and the importance of considering the heterogeneity of trajectories of preschool pain responding when examining the factors that are associated with children's pain-related distress.
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Oral cancer pain is debilitating and understanding mechanisms for it is critical to develop novel treatment strategies treatment strategies. Brain-derived neurotrophic factor (BDNF) signaling is elevated in oral tumor biopsies and is involved with tumor progression. Whether BDNF signaling in oral tumors contributes to cancer-induced pain is not known. ⋯ Last but not the least, intra-TG siRNA for TrkB also reversed tumor-induced orofacial pain behaviors. Our data suggest that TrkB activities on lingual sensory afferents are partly controlled by local release of OSCC-derived BDNF, thereby contributing to oral cancer pain. This is a novel finding and the first demonstration of a peripheral role for BDNF signaling in oral cancer pain.
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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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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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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.