1 3 Rheumatol Int DOI 10.1007/s00296-013-2943-5 SHORT COMMUNICATION Involvement of BDNF in knee osteoarthritis: the relationship with inflammation and clinical parameters Adriano Prado Simão · Vanessa Amaral Mendonça · Tássio Málber de Oliveira Almeida · Sérgio Antunes Santos · Wellington Fabiano Gomes · Candido Celso Coimbra · Ana Cristina Rodrigues Lacerda Received: 3 October 2013 / Accepted: 30 December 2013 © Springer-Verlag Berlin Heidelberg 2014 (p < 0.0001) and fourfold lower than in the plasma of healthy controls (p < 0.0001). Subsequent analyses showed that the plasma BDNF levels significantly cor- related with self-reported pain (Western Ontario and McMaster Universities Osteoarthritis Index) (r s = 0.39, p = 0.04). Furthermore, no correlation was found between the plasma and synovial fluid BDNF concentra- tions and knee OA severity. The findings of this study suggest that systemic BDNF levels are most likely asso- ciated with the mechanism of joint pain in knee OA in the acute stage of joint inflammatory process. Further studies are necessary to address the functional role of BDNF in the modulation of pain to establish new thera- peutic implications. Keywords Brain-derived neurotrophic factor · Knee · Osteoarthritis · Synovial fluid Introduction Osteoarthritis (OA) is a chronic progressive degenerative joint disease that involves not only articular cartilage but also synovium, subchondral bone, and the surrounding mus- cles and ligaments. OA is characterized by cartilage destruc- tion, subchondral bone sclerosis, and osteophyte or cyst for- mation. Knee osteoarthritis is a major cause of severe pain, joint stiffness, limited motion, and disability [1, 2]. Previ- ous studies have suggested that neurotrophins are involved in arthritic processes [3–6]. The neurotrophin brain-derived neurotrophic factor (BDNF) is reported to be involved in the joint inflammatory process, and its production is increased in response to pro-inflammatory cytokines [4]. The role of neurotrophins as important factors in arthritis has been discussed previously [4, 7]. High BDNF mRNA Abstract The aim of this study was to analyze the lev- els of brain-derived neurotrophic factor (BDNF) in both the plasma and synovial fluid of patients with primary knee osteoarthritis compared with control individuals and to investigate the relationship between BDNF levels and self-reported pain. Twenty-seven patients with knee oste- oarthritis (OA) and 19 healthy subjects were enrolled in the study. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. Radiographic grading of OA in the knee was performed using the Kellgren–Lawrence criteria. The BDNF lev- els in the plasma and synovial fluid were measured by enzyme-linked immunosorbent assay. The mean plasma BDNF levels of the knee OA patients were significantly higher than that of the healthy controls (2,378 ± 1,067.2 vs. 1,756 ± 804.3 pg/mL, p < 0.05). BDNF levels in the synovial fluid of OA patients (358.9 ± 178.4 pg/mL) were sixfold lower than in corresponding blood samples A. P. Simão · V. A. Mendonça · T. M. de Oliveira Almeida · W. F. Gomes · A. C. R. Lacerda Integrated Center for Graduate Studies and Research Health (CIPq-Health), Federal University of Jequitinhonha and Mucuri Valleys (UFVJM), Diamantina, Minas Gerais, Brazil A. P. Simão (*) Nursing School, Physiotherapy Course, Federal University of Alfenas (UNIFAL), Av. Jovino Fernandes Sales, 2600, Alfenas, Minas Gerais 37130-000, Brazil e-mail: adrianopsimao@ig.com.br S. A. Santos Hospital Nossa Senhora da Saúde, Diamantina, Minas Gerais, Brazil C. C. Coimbra Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil