ABSTRACT
BACKGROUND: Neuropathic back pain is mediated, at least partially, by N-methyl-D-aspartate (NMDA) receptors. Nitrous oxide (N2O) is an NMDA receptor antagonist. We therefore tested the primary hypothesis that patients receiving N2O have lower pain scores after epidural steroid injection than patients not receiving N2O. METHODS: Patients with recurrent low back pain scheduled for epidural steroid blocks were randomly assigned to receive either oxygen (O2, n = 39) or the combination of 50% O2 and 50% N2O during and after each block (N2O, n = 39). Before each injection and at a 3-month follow-up visit, patients completed questionnaires: Oswestry survey, 12-Item Short Form Health Survey questionnaire, Leeds Assessment of Neuropathic Symptoms and Signs pain scale, and Visual Analog Scale. Total opioid use per 24 hours was recorded. The serum samples for tumor necrosis factor-α, interleukin (IL)-6, interferon-γ, IL-10, IL-17A, and IL-1ß assays were collected at every visit and evaluated. Standard descriptive statistics were used to compare the randomized groups on baseline variables. Any imbalanced covariates with an absolute standardized difference >0.44 were adjusted for in both primary and secondary analyses. Both modified intention-to-treat and per-protocol analyses were conducted for our outcomes. Our secondary analyses were per protocol. RESULTS: in patients given N2O (mean [SD], -1.6 [3.0] cm) and O2 (-1.2 [2.6] cm), with difference -0.13 (95% confidence interval: -1.43, 1.17), N2O - O2; P = 0.84. No difference was found between the 2 randomized groups on changes in Leeds Assessment of Neuropathic Symptoms and Signs pain score, Oswestry score, or 12-Item Short Form Health Survey from baseline, or in satisfaction with the procedure, satisfaction with pain treatment, or use of opioid overtime. Overall, no significant differences on any cytokine were found between the 2 groups. The estimated odds ratios of taking opioid was 0.46 (0.12, 1.84) (N2O versus O2; P = 0.12). CONCLUSIONS: N2O administration did not improve pain or psychological or physical aspects of health-related quality of life. N2O does not appear to be an effective treatment for chronic neuropathic back pain.
