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      Contribution of Infrapatellar Fat Pad and Synovial Membrane to Knee Osteoarthritis Pain

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          Abstract

          Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and disability in the adult population. Interestingly, there are patients with symptomatic OA displaying pain, while patients with asymptomatic OA that do not experience pain but show radiographic signs of joint damage. Pain is a complex experience integrating sensory, affective, and cognitive processes related to several peripheral and central nociceptive factors besides inflammation. During the last years, the role of infrapatellar fat pad (IFP), other than the synovial membrane, has been investigated as a potential source of pain in OA. Interestingly, new findings suggest that IFP and synovial membrane might act as a functional unit in OA pathogenesis and pain. The present review discuss the role of IFP and synovial membrane in the development of OA, with a particular focus on pain onset and the possible involved mediators that may play a role in OA pathology and pain mechanisms. Inflammation of IFP and synovial membrane may drive peripheral and central sensitization in KOA. Since sensitization is associated with pain severity in knee OA and may potentially contribute to the transition from acute to chronic, persistent pain in knee OA, preventing sensitization would be a potentially effective and novel means of preventing worsening of pain in knee OA.

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          The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis

          Osteoarthritis (OA) is the most common chronic disease of human joints. The basis of pathologic changes involves all the tissues forming the joint; already, at an early stage, it has the nature of inflammation with varying degrees of severity. An analysis of the complex relationships indicates that the processes taking place inside the joint are not merely a set that (seemingly) only includes catabolic effects. Apart from them, anti-inflammatory anabolic processes also occur continually. These phenomena are driven by various mediators, of which the key role is attributed to the interactions within the cytokine network. The most important group controlling the disease seems to be inflammatory cytokines, including IL-1 β , TNF α , IL-6, IL-15, IL-17, and IL-18. The second group with antagonistic effect is formed by cytokines known as anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of OA with respect to inter- and intracellular signaling pathways is still under investigation. This paper summarizes the current state of knowledge. The cytokine network in OA is put in the context of cells involved in this degenerative joint disease. The possibilities for further implementation of new therapeutic strategies in OA are also pointed.
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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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              Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score).

              In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools, integrating expert readers' experience with all available scoring tools and the published data comparing the different scoring systems, we iteratively developed the magnetic resonance imaging (MRI) Osteoarthritis Knee Score (MOAKS). The purpose of this report is to describe the instrument and its reliability. The MOAKS instrument refines the scoring of bone marrow lesions (BMLs) (providing regional delineation and scoring across regions), cartilage (sub-regional assessment), and refines the elements of meniscal morphology (adding meniscal hypertrophy, partial maceration and progressive partial maceration) scoring. After a training and calibration session two expert readers read MRIs of 20 knees separately. In addition, one reader re-read the same 20 MRIs 4 weeks later presented in random order to assess intra-rater reliability. The analyses presented here are for both intra- and inter-rater reliability (calculated using the linear weighted kappa and overall percent agreement). With the exception of inter-rater reliability for tibial cartilage area (kappa=0.36) and tibial osteophytes (kappa=0.49); and intra-rater reliability for tibial BML number of lesions (kappa=0.54), Hoffa-synovitis (kappa=0.42) all measures of reliability using kappa statistics were very good (0.61-0.8) or reached near-perfect agreement (0.81-1.0). Only intra-rater reliability for Hoffa-synovitis, and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement <75%. MOAKS scoring shows very good to excellent reliability for the large majority of features assessed. Further iterative development and research will include assessment of its validation and responsiveness. Copyright © 2011 Osteoarthritis Research Society International. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2019
                31 March 2019
                : 2019
                : 6390182
                Affiliations
                1Musculoskeletal Pathology and Oncology Laboratory, Department of Orthopaedics and Orthopaedic Oncology, University of Padova, Padova, Italy
                2Institute of Human Anatomy, Department of Neuroscience, University of Padova, Italy
                3L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region, Via N. Giustiniani 2, 35128 Padova, Italy
                4Clinica Medica 3, Department of Medicine, DIMED, University of Padova, Italy
                5Department of Orthopaedics and Orthopaedic Oncology, University of Padova, Padova, Italy
                6Rheumatology Unit, Department of Medicine, DIMED, University Hospital of Padova, Italy
                Author notes

                Academic Editor: Magali Cucchiarini

                Author information
                http://orcid.org/0000-0003-1129-2574
                http://orcid.org/0000-0003-4572-622X
                http://orcid.org/0000-0001-9905-0363
                http://orcid.org/0000-0003-3025-4717
                http://orcid.org/0000-0003-4327-2500
                http://orcid.org/0000-0002-1079-6669
                Article
                10.1155/2019/6390182
                6462341
                4ba53e04-f3c0-4cea-b519-e5373b7b181e
                Copyright © 2019 Elisa Belluzzi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 November 2018
                : 26 February 2019
                : 14 March 2019
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                Review Article

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