Background and objectives: Pain neuroscience education (PNE) is a therapeutic strategy aimed at reconceptualizing pain in patients with chronic low back pain (CLBP). This systematic review with a meta-analysis (SRMA) aimed to assess the effectiveness of PNE in reducing pain, disability, kinesiophobia, and catastrophizing in patients with CLBP at the end of the intervention, and at 1 and 3 months of follow-up. Materials and Methods: Following PRISMA guidelines, an SRMA was conducted after searching in PubMed Medline, Scopus, Web of Science, and PEDro databases from inception up to June 2025. The inclusion criteria agreed with the PICOS tool: population (patients with CLBP), intervention (PNE), comparator (physiotherapy or non-intervention), outcomes (pain, disability, kinesiophobia, and catastrophizing), and study design (randomized controlled trials (RCTs) and pilot RCTs). The PEDro scale was used to assess the methodological quality and risk of bias of the RCTs included. The pooled effect was assessed using the Cohen standardized mean difference (SMD) and its 95% confidence interval (95% CI) in a random-effects model. Results: Fifteen RCTs, including data from 810 patients (43.7 ± 5.2 years; 61% female) with CLBP were included. The mean methodological quality of the RCTs included was good (6.8 ± 1.1 on the PEDro scale). Selection, performance, and detection were the most important biases identified. Our meta-analysis demonstrated, at the end of the intervention, and at 1 and 3 months of follow-up, respectively, that PNE is effective in reducing pain intensity (SMD = −0.65, p = 0.005; SMD = −1.1, p < 0.001; SMD = −1; p < 0.001), disability (SMD = −0.6, p = 0.009; SMD = −0.78, p = 0.002; SMD = −0.84; p = 0.004), and kinesiophobia (SMD = −1.12, p < 0.001; SMD = −1.51, p < 0.001; SMD = −1.57; p = 0.001). In reducing catastrophizing, PNE was largely effective at the end of intervention (SMD = −0.9, p = 0.016) and at 1 month of follow-up (SMD = −1.36, p = 0.007). Conclusions: Our findings demonstrate that PNE is an effective therapeutic approach for the management of CLBP, reducing pain, disability, kinesiophobia, and catastrophizing in patients with CLBP.
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