The Therapeutic Effect of Saline in Lumbar Injection Trials: A Systemic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract

Background: Normal saline is commonly used as a presumed inert placebo control in lumbar injection trials. However, prior studies suggest that saline injections may be associated with improvements in patient-reported outcomes, potentially confounding interpretation of comparative treatment effects. The magnitude, durability, and clinical relevance of these changes have not been systematically characterized. The primary aim of this study was to evaluate changes in patient-reported outcomes following saline injection in patients with lumbar radiculopathy and, separately, in patients with diskogenic low back pain.

Methods: A systematic review of PubMed, Embase, and Google Scholar was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify randomized controlled trials (RCTs) published between 2000 and 2025 that included a saline injection arm for lumbar radiculopathy or diskogenic pain. Within-arm pre-post changes in Visual Analog Scale (VAS) pain scores and Oswestry Disability Index (ODI) were pooled. Outcomes were evaluated at multiple time points up to 1 year. Subgroup analyses were performed based on injection route. Changes were contextualized relative to established minimal clinically important difference (MCID) thresholds.

Results: Eighteen RCTs comprising 759 patients were included. In lumbar radiculopathy, saline arms demonstrated statistically significant reductions in leg pain and disability across all evaluated time points. Pooled mean differences for leg pain VAS ranged from -1.79 at 1 month to -3.85 at 1 year, while ODI improvements increased from -7.30 to -17.83 points over the same interval, exceeding MCID thresholds. Improvements were more consistent following epidural injection. By contrast, patients with diskogenic pain exhibited smaller changes in back pain and disability, with most pooled estimates failing to reach MCID thresholds.

Conclusions: Saline injection arms of lumbar injection RCTs demonstrate meaningful improvements in pain and disability over time, particularly in patients with lumbar radiculopathy. These findings suggest that saline injections are not inert comparators and may elevate baseline response in interventional trials, potentially obscuring the incremental benefit of active injectates. Future RCTs should consider incorporating nonsaline control arms to better isolate treatment-specific effects and improve interpretability of comparative outcomes.

Level of evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.