Articles: pain-management.
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Anesthesia and analgesia · Dec 2024
The Influence of Pharmacogenetic Factors on the Pharmacokinetics of Morphine and Its Metabolites in Pediatric Patients: A Systematic Review.
Morphine is a potent analgesic used for treating surgical and cancer pain. Despite being the drug of choice for the management of severe pain in children, the high interindividual variability in morphine pharmacokinetics limits its clinical utility to effectively relieve pain without adverse effects. This review was conducted to identify and describe all studies that have assessed the effect of genetic factors on the pharmacokinetics of morphine and its main metabolites in children. ⋯ Variants of the genes SLC22A1 and ABCC3 had the most supporting evidence for genetic variants that influence morphine and morphine metabolites pharmacokinetics. Although the available evidence suggests a potential genetic contribution to the variability in morphine concentration, the heterogeneity of the included studies in terms of experimental design and small sample sizes in some studies makes it challenging to propose the use of genetic biomarkers to personalize morphine dosing. This underscores the need to conduct more comprehensive and large-scale pharmacokinetic-pharmacogenetic studies to determine how or if genetic testing can optimize morphine safety and effectiveness in children.
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Fibromyalgia syndrome (FMS) is a debilitating widespread chronic pain condition of unclear pathophysiology. We studied small noncoding RNAs as potential classifiers and mediators of FMS. Blood and keratinocyte microRNAs (miRs) and transfer RNA fragments (tRFs) were profiled by small RNA-sequencing within a comprehensively phenotyped female cohort of 53 patients with FMS vs 34 healthy controls (hCOs) and 15 patients with major depression and chronic physical pain (disease controls). ⋯ In blood, altered small RNAs were linked to immune and RNA processes, whereas in keratinocytes, adhesion and epithelial functions were targeted. Modulated tRFs shared sequence motifs in patients with FMS, which may promote concerted pathway regulation. Our findings show miRs/tRFs as key small RNAs dysregulation in FMS pathophysiology and open new perspectives for FMS diagnostics, symptom monitoring, and clinical management.