Abstract

Background:Ankylosing spondylitis (AS) is a chronic rheumatic disease that manifests itself in a range of inflammatory changes, severe pain and rapid progression with the development of osteoproliferation and the formation of ankylosis. Prerequisites are created for the emergence of signs of central sensitization. Scientists are growing interested in the role of the phenomenon of central sensitization. Central sensitization is present in almost half of patients with chronic pain (45% SpA, 41% RA, 62% OA and 94% of FM patients) [1]. Brain neurotrophic factor (BDNF) is involved in pain regulation mechanisms and the occurrence of central sensitization, but its role in patients with AS is poorly understood.Objectives:Our study aimed to determine levels of plasma BDNF in patients with AS and evaluate their role as central sensitization predictors in patients with ankylosing spondylitis.Methods:We examined 143 patients with AS according to modified New York criteria (26 women and 117 men) with mean age 42.1±11.3 years (M±σ) and 35 persons of the control group, representative by age, sex. The content of plasma BDNF was determined at 8:00 and 20:00 by ELISA and calculated the daily average and morning/evening ratio - 8:00/20:00 BDNF index. All patients completed self-administered questionnaire Fibromyalgia Rapid Screening Tool (FiRST) to detect FM. FM was defined by a score = > 5/6 by the FiRST. The study was conducted in compliance with bioethical standards. All data were analyzed using IBM Statistics SPSS 22.Results:Among 143 patients with AS, there were 51 persons with FiRST ≥ 5, indicating central sensitization and probable FM. In the group with AS mean scores (M±σ) of plasma BDNF levels were 962.5±357.2 pg/ml at 8:00 and 834.7±510.0 pg/ml at 20:00 compared to control group (785.2±109.7 pg/ml and 450.6±358.9 pg/ml; p< 0.001). 36% AS patients were with + FiRST and had higher daily average and evening BDNF levels and a decreased 8:00/20:00 BDNF index. According to 8:00/20:00 BDNF index, we divide AS patients into 4 groups: 1st quartile (Q1) included people with BDNF index <0.83; 2nd quartile (Q2) - 0.83 - 1.15; 3rd quartile (Q3) - 1.16 - 2.49; 4th quartile (Q4) - > 2.49. Table 1 shows detailed information about FM’s quantitative characteristics in patients with AS (n = 143) depending on the 8:00/20:00 BDNF index.Table 1.Quantitative characteristics of FM in patients with AS (n = 143) depending on the 8:00/20:00 BDNF index.ParametersBDNF «8:00 / 20:00»< 0.830,83 – 1.151,16 – 2.49> 2.49Q1 (n=37)Q2 (n=35)Q3 (n=35)Q4 (n=36)FiRST (M±σ)4.49±1,464.23±1.423.03±1.442.81±1.04***#***#FiRST≥ 5, n (%)24 (64,9 %)17 (48.6 %)9 (25.7 %)1 (2.78 %)***#***#Notes: 1. * - statistically significant differences relative to Q1 (* - p <0.05;** - p <0.01; *** - p <0.001); 2. # - statistically significant differences relative to Q2 (# - p <0.05).In patients with AS and + FiRST was registered an inadequate decrease in plasma BDNF levels in the evening, as evidenced by a decrease in the 8:00/20:00 BDNF index, which was combined with increased disease activity and poorer of the functional status.The ROC analysis results showed that the 8:00/20:00 BDNF index at the cut-off point of 0.95 confirms the presence of central sensitization in patients with AS with a sensitivity of 86.2% and a specificity of 79.6%. The AUC is 0.878, which indicates a good quality of the model. Patients with the 8:00/20:00 BDNF index <0.95 are many times more likely to detect features of central sensitization (OR = 20.9; 95% CI: 8.66-50.39, p < 0.001).Conclusion:Our results showed high diagnostic value to determine plasma levels of BDNF and to calculate 8:00/20:00 BDNF index as central sensitization marker in patients with AS with a sensitivity of 86.2% and a specificity of 79.6%.

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