The neurotoxic effect of opioid has not been thoroughly described. No studies have been conducted to explain the effect of opioids in chronic non-cancer pain therapy on the neurotrophic factors level. Due to the ability to cross the blood-brain barrier, it seems the determination of serum Brain-derived neurotrophic factor (BDNF) concentration is a reliable presentation of the concentration in the central nervous system. The aim of the study was to explore the changes of plasma BDNF concentration during long-term opioid therapy. The study group included 28 patients with chronic low back pain treated with opioid therapy buprenorphine (n=10), tramadol (n=8), oxycodone (n=6), morphine (n=3), fentanyl (n=1). The control group included 11 patients. Measurements of plasma BDNF concentrations were performed, and information about opioid therapy were recorded (age, sex, opioid substance type, daily dose and the duration of opioid therapy). Data were analyzed using nonparametric tests. The median BDNF level in the study group was significantly lower (2.73 ng/mL) than that in the control group (5.04 ng/mL, <0.05). BDNF levels did not differ among groups based on the type of opioid substance used, but the lowest median value was observed for tramadol (2.62 ng/mL), and the highest median value was observed for buprenorphine (2.73 ng/mL). The widest minimum-maximum ranges of BDNF for oxycodone were noted, minimum 1.23 ng/mL and maximum 4.57 ng/mL, respectively. BDNF concentrations were correlated with age in the tramadol group and with the duration of opioid therapy in the buprenorphine group. Chronic opioid therapy for noncancer pain induces specific changes in the BDNF concentration. Tramadol and buprenorphine exerted an important effect on BDNF levels in the examined patients. The BDNF level depends on duration of opioid therapy with buprenorphine, and age in tramadol therapy.