Structural and Functional Treatment of Persistent Spinal Pain Syndrome Type 2: A Fibrosis-Stratified Network Meta-Analysis of Epidural Adhesiolysis and Neuromodulation.

Background/Objectives: Persistent spinal pain syndrome type 2 (PSPS-T2) is treated with two mechanistically distinct interventional families: epidural adhesiolysis (EA), directed at structural epidural pathology, and neuromodulation (NM), directed at modulation of nociceptive signaling. Epidural fibrosis is a biologically plausible candidate for treatment stratification, but whether it independently modifies treatment response remains unproven. This study reviewed the available evidence to determine both the comparative findings and the limitations imposed by the current evidence architecture. Methods: A PROSPERO-registered systematic review and frequentist random-effects network meta-analysis were performed. Studies were classified at the study level, rather than the individual-patient level, as fibrosis-positive (structurally confirmed) or unselected (without confirmed fibrosis). Treatment effects were synthesized separately within each stratum, and an exploratory study-level meta-regression evaluated fibrosis status as a potential moderator. Results: The final dataset comprised 87 studies including 33,504 patients: 40 fibrosis-positive studies (n = 4180) and 47 fibrosis-unselected studies (n = 29,324). Treatment family and fibrosis status were almost completely confounded. EA was evaluated almost exclusively in fibrosis-positive cohorts, whereas NM was evaluated almost exclusively in fibrosis-unselected studies. Although pooled improvements in pain (-0.97 vs. -0.63) and disability (-11.01 vs. -8.46) were greater in fibrosis-positive studies, these differences cannot be attributed independently to fibrosis. Residual heterogeneity remained substantial (I2 71-92%). Peripheral nerve field stimulation and EA protocols incorporating steroid, hyaluronidase, and hypertonic saline achieved the highest probability score for pain relief. All probability scores for the treatments should be interpreted as exploratory. Conclusions: Discordance between EA and NM in PSPS-T2 stems from structurally different populations, precluding pooled comparative classifications or claims that fibrosis modifies treatment effect. While fibrosis remains a promising candidate stratifier, proving it requires prospective trials that stratify randomization to EA versus NM following standardized fibrosis assessment.