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The application value of repeated intra-articular pulsed radiofrequency for the treatment of knee joint pain has remained to be determined. To investigate this, a total of 64 patients with chronic knee joint pain admitted to Caoxian People's Hospital (Caoxian, Chine) between October 2016 and May 2018 were enrolled in the present study and analyzed prospectively. The patients were randomly divided into a control group, receiving treatment with a single intra-articular pulsed radiofrequency through the knee joint (n=32), and an experimental group, receiving multiple intra-articular pulsed radiofrequency treatments through the knee joint (n=32). The visual analog scale score (VAS), clinical efficacy and adverse reactions prior to and after treatment were compared between the two treatments. Synovial fluid cytokines were measured using ELISA prior to and after treatment. After the treatment, the control group and the experimental group both had a lower VAS (P<0.001) and the control group had a higher VAS and lower pain relief than the experimental group (P<0.001). The control group had a total effectiveness rate of 78.13%, with 13 patients experiencing complete relief (40.63%), 12 patients exhibiting a marked improvement (37.5%) and 7 patients reporting no effects (21.87%). The experimental group had a total effectiveness rate of 90.63%, with 18 patients (56.25%) being cured, 11 patients having a marked effect (34.37%) and 3 patients reporting no effects (9.38%). The experimental group had a higher incidence of adverse reactions than the control group (P<0.05). After treatment, the two groups had decreased IL-6, IL-10 and TNF-α levels in the knee joint synovial fluid (P<0.05), with the experimental group having lower cytokine levels than the control group (P<0.05). These results indicated that repeated intra-articular pulsed radiofrequency is an effective method for the treatment of knee joint pain and may be used in clinical practice. [ABSTRACT FROM AUTHOR]