BackgroundKnee osteoarthritis (OA) is a multifactorial form of rheumatic condition contributing to physical and psychological factors. Treatments have been provided solely and often compared with each other. An alternative view is that combined treatments addressing physical and psychological factors may result in more benefits. This study aimed to investigate the effect of pain neuroscience education (PNE) followed by Pilates exercises (PEs) in participants with knee OA, compared to PE alone.MethodsIn this two-arm assessor-blind pilot randomized controlled trial, fifty-four community-dwelling adults with knee OA were randomly assigned to the PNE followed by PEs and PEs groups (27 in each group). The study was conducted between early July 2021 and early March 2022 at the university’s health center. Primary outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales of pain and physical limitation and secondary outcomes were Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, Pain Self-Efficacy Questionnaire, and Timed "Up & Go" test covering function. The primary and secondary outcomes were measured at baseline and eight weeks post-treatment. A general linear mixed model was used for between-group comparison with a statistical significance level of 0.05.ResultsSignificant within-group differences were observed in all outcomes in both groups at post-treatment. There were no statistically between-group differences in pain (adjusted mean difference: -0.8; 95% CI -2.2 to 0.7;p= 0.288), physical limitation (adjusted mean difference: -0.4; 95% CI -4 to 3.1;p= 0.812) and function (adjusted mean difference: -0.8; 95% CI -1.8 to 0.1;p= 0.069) at eight weeks. For pain catastrophizing (adjusted mean difference: -3.9; 95% CI -7.2 to -0.6;p= 0.021), kinesiophobia (adjusted mean difference: -4.2; 95% CI -8.1 to -0.4;p= 0.032), and self-efficacy (adjusted mean difference: 6.1; 95% CI 0.7 to 11.5;p= 0.028) statistically between-group improvements were observed favoring PNE followed by PEs group after the treatment.ConclusionsCombining PNE with PEs could have superior effects on psychological characteristics but not on pain, physical limitation, and function, compared to PEs alone. This pilot study emphasizes the need to investigate the combined effects of different interventions.Trial registrationIRCT20210701051754N1.