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      Nuevas dianas terapéuticas en dolor por artrosis Translated title: New pharamcological targets for osteoarthritis induced pain

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          Abstract

          RESUMEN La artrosis puede provocar la aparición de un proceso doloroso que es, hasta cierto punto, independiente de la patología, dado que su aparición y evolución no están directamente relacionadas con la progresión de la enfermedad. Estas características diferenciales hacen que el tratamiento del dolor por artrosis pueda tener y requerir un abordaje particular. La evidencia creciente del papel de la inflamación, sinovitis, en este dolor ha supuesto un aumento de la investigación destinada a identificar nuevas dianas farmacológicas relacionadas con este proceso. Entre las dianas que han ido descubriéndose a lo largo de los últimos años, pueden destacarse la PGE2 (liberada por los osteoblastos, y que aumentan la expresión de canales Nav1.8), determinados miARN y receptores TLR (activados por la sinovitis y que facilitan la transmisión de la señal nociceptiva) y el factor de crecimiento nervioso (NGF), que, mediante su unión al receptor trkA, contribuye a la sensibilización periférica y a la cronificación del dolor. Estas son solo algunas de las más prometedoras dianas farmacológicas para el tratamiento del dolor asociado a la artrosis que tal vez puedan, algún día, poner remedio al dolor de los pacientes aquejados de esta enfermedad.

          Translated abstract

          ABSTRACT Osteoarthritis can be accompanied by a painful process that is mainly independent of the pathology, since its appearance and evolution are not directly related to the progression of the disease. These differential characteristics mean that the treatment of osteoarthritis pain may require a differential approach. The growing evidence of the role of inflammation, synovitis, in this osteoarthritis related-pain has led to an increase in research aimed at identifying new drug targets. Among those that have been identified in recent years, we can highlight PGE2 (released by osteoblasts, and that can increase the expression of Nav1.8 channels), certain miRNAs and TLR receptors (activated by synovitis and which facilitate the transmission of the nociceptive signal) and nerve growth factor (NGF), which, through its binding to the trkA receptor, contributes to peripheral sensitization and chronic pain. These are just some of the most promising drug targets for osteoarthritis pain that may one day be able to remedy the pain of osteoarthritis patients.

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          Most cited references44

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          The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.

          Osteoarthritis (OA), one of the most common rheumatic disorders, is characterized by cartilage breakdown and by synovial inflammation that is directly linked to clinical symptoms such as joint swelling, synovitis and inflammatory pain. The gold-standard method for detecting synovitis is histological analysis of samples obtained by biopsy, but the noninvasive imaging techniques MRI and ultrasonography might also perform well. The inflammation of the synovial membrane that occurs in both the early and late phases of OA is associated with alterations in the adjacent cartilage that are similar to those seen in rheumatoid arthritis. Catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E(2) and neuropeptides are produced by the inflamed synovium and alter the balance of cartilage matrix degradation and repair, leading to excess production of the proteolytic enzymes responsible for cartilage breakdown. Cartilage alteration in turn amplifies synovial inflammation, creating a vicious circle. As synovitis is associated with clinical symptoms and also reflects joint degradation in OA, synovium-targeted therapy could help alleviate the symptoms of the disease and perhaps also prevent structural progression.
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            Functional significance of macrophage-derived exosomes in inflammation and pain.

            Exosomes, secreted microvesicles transporting microRNAs (miRNAs), mRNAs, and proteins through bodily fluids, facilitate intercellular communication and elicit immune responses. Exosomal contents vary, depending on the source and the physiological conditions of cells, and can provide insights into how cells and systems cope with physiological perturbations. Previous analysis of circulating miRNAs in patients with complex regional pain syndrome (CRPS), a debilitating chronic pain disorder, revealed a subset of miRNAs in whole blood that are altered in the disease. To determine functional consequences of alterations in exosomal biomolecules in inflammation and pain, we investigated exosome-mediated information transfer in vitro, in a rodent model of inflammatory pain, and in exosomes from patients with CRPS. Mouse macrophage cells stimulated with lipopolysaccharides secrete exosomes containing elevated levels of cytokines and miRNAs that mediate inflammation. Transcriptome sequencing of exosomal RNA revealed global alterations in both innate and adaptive immune pathways. Exosomes from lipopolysaccharide-stimulated cells were sufficient to cause nuclear factor-κB activation in naive cells, indicating functionality in recipient cells. A single injection of exosomes attenuated thermal hyperalgesia in a murine model of inflammatory pain, suggesting an immunoprotective role for macrophage-derived exosomes. Macrophage-derived exosomes carry a protective signature that is altered when secreting cells are exposed to an inflammatory stimulus. We also show that circulating miRNAs altered in patients with complex regional pain syndrome are trafficked by exosomes. With their systemic signaling capabilities, exosomes can induce pleiotropic effects potentially mediating the multifactorial pathology underlying chronic pain, and should be explored for their therapeutic utility. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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              MicroRNA in osteoarthritis: physiopathology, diagnosis and therapeutic challenge

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                Author and article information

                Journal
                dolor
                Revista de la Sociedad Española del Dolor
                Rev. Soc. Esp. Dolor
                Inspira Network Group, S.L (Madrid, Madrid, Spain )
                1134-8046
                2021
                : 28
                : suppl 1
                : 57-63
                Affiliations
                [1] Madrid Madrid orgnameUniversidad Rey Juan Carlos orgdiv1Facultad Ciencias de la Salud orgdiv2Departamento de Farmacología Spain
                Article
                S1134-80462021000100057 S1134-8046(21)02800000057
                10.20986/resed.2021.3863/2020
                d48c0ae0-549a-46a9-9ffc-31c70ad4e2e0

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 44, Pages: 7
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                SciELO Spain

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                Artículos

                review,dolor,NGF,nuevas dianas,miRNA,rata,rat,revisión,osteoarthritis,pain,Artrosis

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