Randomized trial of intraoperative nitrous oxide for postoperative pain reduction in cervical spinal cord injury

Pain Rep. 2026 Aug 5;11(5):e1473. doi: 10.1097/PR9.0000000000001473. eCollection 2026 Oct.

ABSTRACT

INTRODUCTION: Neuropathic pain after cervical spinal cord injury (SCI) is common and difficult to manage.

OBJECTIVES: To evaluate whether intraoperative nitrous oxide (N₂O) influences acute postoperative pain and long-term neuropathic pain after cervical SCI surgery.

METHODS: This single-center, randomized study enrolled adults (≥20 yr) undergoing emergency surgery for traumatic cervical SCI (American Spinal Injury Association Impairment Scale C or D). Patients were randomly assigned to receive intraoperative N₂O or Air. The primary outcome was resting pain intensity on postoperative day 1 (D1), measured using the Numeric Rating Scale (NRS). Secondary outcomes included global pain and neuropathic pain assessments up to 6 months (6M) after surgery.

RESULTS: Of 80 randomized patients, 59 were analyzed (mean [SD] age 70.34 [12.07] years; 46 [78%] male). Baseline characteristics were similar between groups (Air, n = 29; N₂O, n = 30). The primary outcome was higher in the N₂O group, indicating no acute analgesic effect (NRS on D1: 3.27 [2.69] vs 5.10 [3.06]; P = 0.021). By contrast, at 6M, resting NRS was lower in the N₂O group (1.72 [2.64] vs 0.53 [1.25]; P = 0.030), and numbness-related symptoms also improved. No serious adverse events occurred.

CONCLUSION: Intraoperative N₂O did not reduce acute postoperative pain after cervical SCI surgery. However, exploratory secondary analyses suggested a potential reduction in chronic neuropathic pain at 6 months, supporting the hypothesis that early perioperative modulation of central sensitization may influence pain chronification after SCI.

PMID:42565101 | PMC:PMC13446972 | DOI:10.1097/PR9.0000000000001473