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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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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Randomized Controlled Trial
Social learning pathways in the relation between parental chronic pain and daily pain severity and functional impairment in adolescents with functional abdominal pain.
Having a parent with chronic pain (CP) may confer greater risk of persistence of CP from childhood into young adulthood. Social learning, such as parental modeling and reinforcement, represents one plausible mechanism for the transmission of risk of CP from parents to offspring. Based on a 7-day pain diary in 154 pediatric patients with functional abdominal CP, we tested a model in which parental CP predicted adolescents' daily average CP severity and functional impairment (distal outcomes) via parental modeling of pain behaviors and parental reinforcement of adolescent's pain behaviors (mediators) and adolescents' cognitive appraisals of pain threat (proximal outcome representing adolescents' encoding of parents' behaviors). ⋯ The indirect pathway through parental reinforcing responses to adolescents' pain did not reach significance for either adolescent pain severity or functional impairment. Identifying mechanisms of increased risk of pain and functional impairment in children of parents with CP ultimately could lead to targeted interventions aimed at improving functioning and quality of life in families with CP. Parental modeling of pain behaviors represents a potentially promising target for family-based interventions to ameliorate pediatric CP.
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Interrupting ongoing activities whilst intending to resume them later is a natural response to pain. Whereas this response facilitates pain management, at the same time it may also disrupt task performance. Previous research has shown that activity interruptions by pain impair subsequent resumption of the activity, but not more than pain-irrelevant interruptions. ⋯ Pain catastrophizing did not influence the results. As in previous studies, activity interruptions by pain were shown to impair the resumption of a task that requires keeping to a step sequence, but not more than interruptions by nonpainful stimuli. Potential explanations are discussed.