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nerve growth factor,synovitis

L Xu, L N Nwosu, J J Burston, P J Millns, D R Sagar, P I Mapp, P Meesawatsom, L Li, A J Bennett, D A Walsh, V Chapman
OBJECTIVE: Nerve growth factor (NGF) has a pivotal role in peripheral hyperalgesia and inflammation; anti-NGF antibodies attenuate pain responses in inflammatory pain models, and in people with osteoarthritis (OA) or low back pain. The aim of this study was to characterise the peripheral mechanisms contributing to the analgesic effects of anti-NGF antibody treatment in an established model of joint pain, which mimics key clinical features of OA. DESIGN: Effects of preventative vs therapeutic treatment with an anti-NGF antibody (monoclonal antibody 911: muMab 911 (10 mg/kg, s...
September 2016: Osteoarthritis and Cartilage
Sadaf Ashraf, Karyn S Bouhana, Jed Pheneger, Steven W Andrews, David A Walsh
BACKGROUND: Inflammation is an essential component of arthritis pain. Nerve growth factor (NGF) plays a key role in acute and chronic pain states especially those associated with inflammation. NGF acts through tropomyosin-receptor-kinase A (TrkA). NGF blockade has reduced arthritis pain in clinical trials. We explored the mechanisms within the joint which may contribute to the analgesic effects of NGF by selectively inhibiting TrkA in carrageenan-induced or collagen-induced joint pain behaviour...
2016: Arthritis Research & Therapy
A M Malfait
This review highlights a selection of recently published literature in the area of osteoarthritis biology. Major themes transpiring from a PubMed search covering the year between the 2014 and the 2015 Osteoarthritis Research Society International (OARSI) World Congress are explored. Inflammation emerged as a significant theme, revealing complex pathways that drive dramatic changes in cartilage homeostasis and in the synovium. Highlights include a homeostatic role for CXC chemokines in cartilage, identification of the zinc-ZIP8-MTF1 axis as an essential regulator of cartilage catabolism, and the discovery that a small aggrecan fragment can have catabolic and pro-inflammatory effects through Toll-like receptor 2...
January 2016: Osteoarthritis and Cartilage
Lilian N Nwosu, Paul I Mapp, Victoria Chapman, David A Walsh
OBJECTIVES: Tropomyosin receptor kinase A (TrkA) mediates nociceptor sensitisation by nerve growth factor (NGF), but it is unknown whether selective TrkA inhibition will be an effective strategy for treating osteoarthritis (OA) pain. We determined the effects of a TrkA inhibitor (AR786) on pain behaviour, synovitis and joint pathology in two rat OA models. METHODS: Knee OA was induced in rats by intra-articular monosodium-iodoacetate (MIA) injection or meniscal transection (MNX) and compared with saline-injected or sham-operated controls...
June 2016: Annals of the Rheumatic Diseases
Laura A Stoppiello, Paul I Mapp, Deborah Wilson, Roger Hill, Brigitte E Scammell, David A Walsh
OBJECTIVE: Structural changes of osteoarthritis (OA) may occur in the absence of pain. In this study, we aimed to identify histopathologic features that are associated with symptomatic knee OA. METHODS: Medial tibial plateaus and synovium samples were obtained at the time of total knee replacement (TKR) surgery for OA (advanced OA group) or were obtained postmortem from subjects who had not sought medical attention for knee pain during the last year of life (non-OA control group)...
November 2014: Arthritis & Rheumatology
Sadaf Ashraf, Paul Ian Mapp, James Burston, Andrew John Bennett, Victoria Chapman, David Andrew Walsh
OBJECTIVES: Nerve growth factor (NGF) is a promising analgesic target, particularly in osteoarthritis (OA) where existing therapies are inadequate. We hypothesised that pain responses to NGF are increased in OA joints. Here, NGF-evoked pain behaviour was compared in two rodent models of OA, and possible mechanisms underlying altered pain responses were examined. METHODS: OA was induced in rat knees by meniscal transection (MNX) or intra-articular monosodium iodoacetate injection (MIA)...
September 2014: Annals of the Rheumatic Diseases
Claire Y J Wenham, Philip G Conaghan
Osteoarthritis (OA) is the most common type of arthritis worldwide and rapidly increasing with ageing populations. It is a major source of pain and disability for individuals and economic burden for health economies. Modern imaging, in particular magnetic resonance imaging (MRI), has helped us to understand that OA is a dynamic remodelling process involving all the structures within the joint. Inflammation is common in OA, with a high prevalence of synovitis seen on imaging, and this has been associated with joint pain...
May 2013: Age and Ageing
Hans-Georg Schaible
Pain is a major clinical problem of osteoarthritis (OA). Recently, OA has been thought to be a disease of the whole joint with both destruction of cartilage and inflammatory components such as synovitis and bone marrow lesions. Clinical studies have documented a significant inflammatory soft tissue contribution to the severity and frequency of OA pain. Both clinical and experimental studies have provided evidence for the sensitization of pain pathways during OA, involving pronounced changes in joint nociceptors and changes of the nociceptive processing in the spinal cord, brainstem, and thalamocortical system...
December 2012: Current Rheumatology Reports
Sumihisa Orita, Takana Koshi, Takeshi Mitsuka, Masayuki Miyagi, Gen Inoue, Gen Arai, Tetsuhiro Ishikawa, Eiji Hanaoka, Keishi Yamashita, Masaomi Yamashita, Yawara Eguchi, Tomoaki Toyone, Kazuhisa Takahashi, Seiji Ohtori
BACKGROUND: One of the sources of knee pain in osteoarthritis (OA) is believed to be related to local chronic inflammation of the knee joints, which involves the production of inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin (IL)-6, and nerve growth factor (NGF) in the synovial membrane, and these cytokines are believed to promote pathological OA. In the present study, correlations between proinflammatory cytokines in knee synovial fluid and radiographic changes and functional scores and pain scores among OA patients were examined...
2011: BMC Musculoskeletal Disorders
Christian Barthel, Nataliya Yeremenko, Roland Jacobs, Reinhold E Schmidt, Michael Bernateck, Henning Zeidler, Paul-Peter Tak, Dominique Baeten, Markus Rihl
INTRODUCTION: We previously described the presence of nerve growth factor receptors in the inflamed synovial compartment. Here we investigated the presence of the corresponding nerve growth factors, with special focus on nerve growth factor (NGF). METHODS: mRNA expression levels of four ligands (NGF, brain derived growth factor (BDNF), neurotrophin (NT)-3, NT-4) and their four corresponding receptors (tyrosine kinase (trk) A, trkB, trkC, NGFRp75) were determined in the synovial fluid (SF) cells of 9 patients with rheumatoid arthritis (RA) and 16 with spondyloarthritis (SpA) and compared with 7 osteoarthritis (OA) patients...
2009: Arthritis Research & Therapy
M Rihl, E Kruithof, C Barthel, F De Keyser, E M Veys, H Zeidler, D T Y Yu, J G Kuipers, D Baeten
OBJECTIVE: To investigate whether expression of the four members of the neurotrophin (NT) family and their four corresponding receptors is related to synovial inflammation in patients with spondyloarthritis (SpA). MATERIAL AND METHODS: Synovial fluid (SF) and serum NTs and their receptors were measured by ELISA. Immunohistochemistry was used for synovial tissue biopsy specimens from patients with SpA, rheumatoid arthritis, and osteoarthritis (OA). In SpA synovium, immunoreactivity of the receptors trkA and NGFRp75 was also assessed before and after 12 weeks of treatment with the monoclonal anti-tumour necrosis factor alpha antibody, infliximab...
November 2005: Annals of the Rheumatic Diseases
L Manni, T Lundeberg, P Tirassa, L Aloe
OBJECTIVES: The aim of our study was to investigate the role of cholecystokinin-8 (CCK-8), which is able to induce the synthesis of nerve growth factor (NGF), in the joint inflammation of carrageenan-injected rats. METHODS: Adult rats were injected in the ankle joint with carrageenan, with or without CCK-8 or a CCK receptor antagonist (proglumide), and tissue swelling, NGF levels and NGF mRNA expression were assessed. RESULTS: Expression of NGF and NGF mRNA increased transiently after carrageenan injection...
July 2002: Rheumatology
Z Wu, K Nagata, T Iijima
To study the role of nerve growth factor (NGF) in local inflammation, we investigated the expression of NGF and its receptors, trkA and p75, in the ankle joints of adjuvant-induced arthritic rats. Infiltrated mononuclear cells revealed a positive immunoreactivity for NGF and trkA; they were also positive for immunostaining for W3/25 and ED1, which mainly stain T cells and macrophages, respectively. Changes in the ratios of NGF-positive cells to mononuclear cells showed a relatively similar pattern for trkA-positive cells, which peaked at weeks 2 to 3 after the adjuvant injection...
December 2000: Histochemistry and Cell Biology
K Asai, T Hirano, K Matsukawa, J Kusada, M Takeuchi, T Otsuka, N Matsui, T Kato
Since neovascularization plays an important role in the propagation of rheumatoid synovitis, we analyzed the concentration of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF), a potent angiogenic and chemotactic factor, in the synovial fluid and serum of rheumatoid arthritis (RA) patients. The immunoreactive GLS/PD-ECGF concentrations (mean value +/- S.D.) in synovial fluid, measured by a sandwich enzyme immunoassay, were significantly higher in RA patients than in osteoarthritis (OA) patients (233...
September 17, 1993: Clinica Chimica Acta; International Journal of Clinical Chemistry
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