BACKGROUND: Appropriate management of patients with Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) remains challenging. The need for robust evidence for treatment modalities is urgently pressing. The aim of this systematic review and network meta-analysis (NMA) is to compare different treatment modalities for patients with PSPS-T2 on pain intensity. METHODS: The study protocol was prospectively registered (PROSPERO; CRD42022360160). Four different databases were consulted from database inception to December 18th, 2023. Randomised controlled trials of interventions for PSPS-T2 were included. The revised Cochrane Risk of Bias Tool was used to assess risk of bias. A NMA with standardized mean differences was calculated with pairwise comparisons between all treatment modalities. RESULTS: Here we include 49 studies in the systematic review and 13 in NMA. A high risk of bias is indicated for 65.3% of the studies. Half of the studies investigate neuromodulation (mainly Spinal Cord Stimulation), 16 explore minimal invasive treatment options (predomitly epidural injections), 6 studies focus on conservative treatments (physiotherapy/cognitive training and medication) and 2 on reoperation. Comparison of neuromodulation versus a combination of conservative and minimal invasive options results in an effect size of 0.45 (95% CI 0.14 to 0.76), clearly favouring neuromodulation (z = 2.88; p = 0.004). Additionally, neuromodulation results in a standardised mean difference of 0.36 (95% CI 0.18 to 0.53) compared to placebo/sham (z 4.03; p < 0.0001). No statistically significant difference is found between conservative options and neuromodulation. CONCLUSIONS: Neuromodulation, followed by conservative treatment options, seems to be the most effective treatment option to obtain pain relief in patients with PSPS-T2. Nevertheless, a personalized approach tailored to individual patient needs is essential for optimizing outcomes, since interventions should be adjusted based on the failure or success of prior therapies.

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