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

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

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

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.

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.

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.