Articles: pain-clinics.
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Osteoarthritis (OA) is a highly prevalent and disabling joint disease, characterized by pathological progressive joint deformation and clinical symptoms of pain. Disease-modifying treatments remain unavailable, and pain-mitigation is often suboptimal, but recent studies suggest beneficial effects by inhibition of the voltage-gated sodium channel Na V 1.7. We previously identified compound 194 as an indirect inhibitor of Na V 1.7 by preventing SUMOylation of the Na V 1.7-trafficking protein, collapsin response mediator protein 2. ⋯ We found that the monoiodoacetate model induced (1) increased pain-like behaviors and calcium responses of glutamatergic neurons in the parabrachial nucleus after evoked cold and mechanical stimuli, (2) conditioned place aversion to mechanical stimulation, (3) functional weight bearing asymmetry, (4) increased sodium currents in dorsal root ganglia neurons, and (5) increased calcitonin gene-related peptide-release in the spinal cord. Crucially, administration of 194 improved all these pain-related outcomes. Collectively, these findings support indirect inhibition of Na V 1.7 as an effective treatment of OA-related pain through the inhibition of collapsin response mediator protein 2-SUMOylation via compound 194.
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Anesthesia and analgesia · Dec 2024
Comparative Effectiveness of Analgesia for Early Pain Management After Pediatric Tonsillectomy: A Systematic Review and Network Meta-Analysis.
Timely and effective analgesia after tonsillectomy in children is crucial, but there is currently no consensus on the optimal analgesics. This analysis aimed to identify the most effective for this surgery. ⋯ Based on these results, we would recommend local bupivacaine infiltration or local levobupivacaine infiltration for older children and dexamethasone injection for younger children for early analgesia after tonsillectomy. However, clinicians should choose the optimal analgesic based on the individual child's condition and clinical situation.
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Previous preclinical and translational studies suggest that tissue trauma related to bony fracture and intervertebral disk disruption initiates the formation of pronociceptive antibodies that support chronic musculoskeletal pain conditions. This study tested this hypothesis in the monosodium iodoacetate (MIA) mouse model of osteoarthritis (OA) and extended the findings using OA patient samples. Monosodium iodoacetate was injected unilaterally into the knees of male and female wild-type (WT) and muMT mice (lacking B cells) to induce articular cartilage damage. ⋯ Similarly, intra-articular injection of IgM from patients with OA was pronociceptive in muMT MIA mice and control subject IgM had no effect. Monosodium iodoacetate-injected joints demonstrate elevated levels of complement component 5a (C5a) and C5a receptor blockade using intra-articular PMX-53-reduced sensitization. These data suggest that MIA-treated mice and patients with OA generate pronociceptive antibodies, and further support the pronociceptive autoimmunity hypothesis for the transition from tissue injury to chronic musculoskeletal pain.
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Hand eczema is a highly prevalent skin disease and one of the most common work-related disorders. In up to two-thirds of individuals affected by hand eczema, the disease becomes chronic and results in substantial personal and occupational disability. Manifestations of chronic hand eczema vary in severity and appearance over time, and people with eczema typically experience itch, pain, and a burning sensation. ⋯ Topical and systemic immunomodulatory therapies approved for atopic dermatitis could be used in severe atopic hand eczema and some of them are under clinical development for chronic hand eczema. Additional research is needed to better understand chronic hand eczema subtypes and underlying mechanisms, and the comparative effectiveness and safety of therapies. This Review combines established knowledge with ongoing changes in our understanding of the disease and their implications for prevention, management, and future research.