Pain
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This article, based on 2 companion studies, presents an in-depth analysis of preschoolers coping with vaccination pain. Study 1 used an autoregressive cross-lagged path model to investigate the dynamic and reciprocal relationships between young children's coping responses (how they cope with pain and distress) and coping outcomes (pain behaviors) at the preschool vaccination. ⋯ Summarizing over the 5 path models and post hoc analyses over the 2 studies, novel transactional and longitudinal pathways predicting preschooler coping responses and outcomes were elucidated. Our research has provided empirical support for the need to differentiate between coping responses and coping outcomes: 2 different, yet interrelated, components of "coping." Among our key findings, the results suggest that a preschooler's ability to cope is a powerful tool to reduce pain-related distress but must be maintained throughout the appointment; caregiver behavior and poorer pain regulation from the 12-month vaccination appointment predicted forward to preschool coping responses and/or outcomes; robust concurrent relationships exist between caregiver behaviors and both child coping responses and outcomes, and finally, caregiver behaviors during vaccinations are not only critical to both child pain coping responses and outcomes in the short- and long-term but also show relationships to broader child cognitive abilities as well.
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Clinical trials to test the safety and efficacy of analgesics across all pediatric age cohorts are needed to avoid inappropriate extrapolation of adult data to children. However, the selection of acute pain models and trial design attributes to maximize assay sensitivity, by pediatric age cohort, remains problematic. Acute pain models used for drug treatment trials in adults are not directly applicable to the pediatric age cohorts-neonates, infants, toddlers, children, and adolescents. ⋯ Models and designs of clinical trials of analgesic medications used in the treatment of acute pain in neonates, infants, toddlers, children, and adolescents were reviewed and discussed at an Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) Pediatric Pain Research Consortium consensus meeting. Based on extensive reviews and continuing discussions, the authors recommend a number of acute pain clinical trial models and design attributes that have the potential to improve the study of analgesic medications in pediatric populations. Recommendations are also provided regarding additional research needed to support the use of other acute pain models across pediatric age cohorts.
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Multiple sclerosis (MS) is an autoimmune-inflammatory neurodegenerative disease that is often accompanied by a debilitating neuropathic pain. Disease-modifying agents slow down the progression of multiple sclerosis and prevent relapses, yet it remains unclear if they yield analgesia. We explored the analgesic potential of fingolimod (FTY720), an agonist and/or functional antagonist at the sphingosine-1-phosphate receptor 1 (S1PR1), because it reduces hyperalgesia in models of peripheral inflammatory and neuropathic pain. ⋯ The antihyperalgesic effects of fingolimod were prevented or reversed by the S1PR1 antagonist W146 (1 mg/kg daily, i.p.) and could be mimicked by either repeated or single injection of the S1PR1-selective agonist SEW2871. Fingolimod did not change spinal membrane S1PR1 content, arguing against a functional antagonist mechanism. We conclude that fingolimod behaves as an S1PR1 agonist to reduce pain in multiple sclerosis by reversing central sensitization of spinal nociceptive neurons.
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Humans require the ability to discriminate intensities of noxious stimuli to avoid future harm. This discrimination process seems to be biased by an individual's attention to pain and involves modulation of the relative intensity differences between stimuli (ie, Weber fraction). Here, we ask whether attention networks in the brain modulate the discrimination process and investigate the neural correlates reflecting the Weber fraction for pain intensity. ⋯ Of note, this vigilance-related functional coupling specifically predicted participants' behavioral ability to differentiate pain intensities. Moreover, unique to pain discrimination tasks, the response in the right superior frontal gyrus linearly represented the Weber fraction for pain intensity, which significantly biased participants' pain discriminability. These findings suggest that pain intensity discrimination in humans relies on vigilance-related enhancement in the parieto-thalamic attention network, thereby allowing the prefrontal cortex to estimate the relative intensity differences between noxious stimuli.