Circadian Rhythms Of Plasma Brain-Derived Neurotrophic Factor In Ankylosing Spondylitis Patients: The Fibromyalgia Relationship

BACKGROUND: Ankylosing spondylitis (AS) is characterized by diurnal variability of clinical symptoms, including aggravation of back pain at night and morning stiffness. Brain-derived neurotrophic factor (BDNF) is involved in the mechanisms of pain and circadian regulation. BDNF production may vary in the case of underlying fibromyalgia (FM), which is a common comorbidity in AS patients. Circadian rhythms and clinical/pathogenetic significance of BDNF with underlying AS are still an unresolved question. The study of the issue could make it possible to develop an individual approach to diagnostics and treatment of AS patients. The study aimed to clarify plasma BDNF circadian rhythms in AS patients and to assess the FM involvement in the process.METHODS: We examined one hundred forty-three 42.1 +/- 11.3-year-old (M +/-sigma) AS patients (81.8% males). The diagnosis of AS was established according to the 1984 Modified New York Criteria, and the diagnosis of FM according to mACR2010 criteria. Concomitant FM was diagnosed in 49 (34.3%) AS patients. ELISA twice a day (at 8:00 and 20:00) was used to determine the plasma BDNF. The control group consisted of 35 individuals aged 52.1 +/- 9.14 years (80.0% males) without AS and FM signs. The study was conducted in compliance with the bioethical standards. The IBM Statistics SPSS 22 software (IBM; Armonk, NY, USA) was used for statistical processing of the results.RESULTS: The patients in the control group demonstrated daily fluctuations of plasma BDNF with a decrease of the plasma level in the evening from 785.2 +/- 109.7 pg/mL at 8:00 to 450.6 +/- 358.9 pg/mL at 20:00 (P<0.0001). Compared to the control group, AS patients demonstrated higher BDNF levels at 8:00 and 20:00 (1.23 and 1.85 times, P<0.001) by contrast with decreased 08:00/20:00 index (1.66 +/- 1.20 vs. 1.96 +/- 0.58, P<0.05). With underlying FM, the direction of daily BDNF fluctuations in AS patients changed - from elevated evening readings to decreases figures of 8:00/20:00 Index. BDNF disturbance was statistically significantly associated with the aggravated manifestation of polysymptomatic distress, pain syndrome, insomnia, and fatigue.CONCLUSIONS: AS patients demonstrated diurnal fluctuations of plasma BDNF that depended on age, sex, and FM comorbidity. Disturbance of plasma BDNF circadian rhythms was associated with aggravated severity of polysymptomatic distress and FM.