Pain
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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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Low back pain (LBP) is a major health challenge globally. Research has identified common trajectories of pain over time. We aimed to investigate whether trajectories described in 1 primary care cohort can be confirmed in another, and to determine the prognostic value of factors collected 5 years prior to the identification of the trajectory. ⋯ Lower social class and higher pain intensity were significantly associated with a more severe trajectory 5 years later, as were patients' perceptions of the greater consequences and longer duration of pain, and greater passive behavioural coping. Low back pain trajectories identified previously appear generalizable. These allow better understanding of the long-term course of LBP, and effective management tailored to individual trajectories needs to be identified.
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Pain and frailty are both prevalent and have severe health impacts among older adults. We conducted a cross-sectional observational study to examine the association between pain and frailty, and depression as a mediator and its interaction with pain on frailty among 1788 Chinese community-dwelling older adults. Physical frailty, pain intensity, and depressive symptoms were assessed using the Frailty Phenotype, the Faces Pain Scale-revised, and the 5-item Geriatric Depression Scale, respectively. ⋯ The relative excess risk of interaction, the attributable proportion due to interaction, and the synergy index (S) were 4.08, 0.50, and 2.34, respectively. These findings suggest that the positive association of pain with frailty is persistent and partially mediated by depression, and comorbid depression and pain have an additive interaction on physical frailty. It has an implication of multidisciplinary care for frail older adults with 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.