Nitrous oxide for the treatment of complex regional pain syndrome: a randomized blinded trial.

INTRODUCTION: Complex Regional Pain Syndrome (CRPS) is a debilitating neuropathic condition often refractory to conventional treatments. N-methyl-D-aspartate (NMDA) receptor antagonists have a well-established role in the development and modulation of chronic neuropathic pain. Nitrous oxide is widely used and generally safe anesthetic gas with NMDA receptor antagonist activity. We therefore tested the hypothesis that brief periods of nitrous oxide exposure reduce pain in patients with CRPS. METHODS: Patients with a diagnosis of CRPS were randomized to either 2 hours of nitrous oxide exposure on three alternating days (Nitrous Oxide) versus a placebo air/oxygen mixture (Air-Oxygen). Our primary outcome was patient-reported pain scores at 1 week and 1 month. Secondary and exploratory outcomes were physical and mental health (PRMOIS-29 v2 survey), specific neuropathic pain symptoms (McGill short-form questionnaire), and opioid consumption. RESULTS: 44 patients participated in the study; 20 were randomized to Nitrous Oxide and 24 were assigned to Air-Oxygen. Pain scores did not differ significantly, with the estimated difference in means (Nitrous Oxide-Air-Oxygen) of -0.57 (95% CI: -1.42 to 0.28) points, p=0.19. There were also no differences detected in secondary outcomes, with the estimated difference in mean Z-scores for physical health (Nitrous Oxide-Air-Oxygen) of 0.13 (95% CI: -0.16 to 0.43), mental health 0.087 (95% CI: -0.31 to 0.48), and Patient Global Impression of Change score -0.7 (95% CI: -1.85 to 0.46). CONCLUSIONS: Compared with air/oxygen, 2 hours of nitrous oxide/oxygen exposure for three sessions did not provide meaningful therapeutic potential for patients with chronic CRPS. Our results do not support using nitrous oxide for the treatment of CRPS.

A rat model to investigate quality of recovery after abdominal surgery.

INTRODUCTION: Major advances in therapies to optimize recovery after surgery have been limited by the lack of an animal model that can mimic major domains of postoperative sickness behavior in humans. We hypothesized that the integration of commonly impaired domains of quality of recovery in humans could be reproduced in a rat model. OBJECTIVES: To create a rat model that can mimic surgical recovery in humans. METHODS: Adult male Sprague-Dawley rats were used in the development of a quality of recovery score after surgery. Six physiological parameters or behaviors were tested in naive, sham, and laparotomized animals. A quality of recovery score was constructed and ranged from 18 (no impairment) to 0 (gross impairment). We treated animals with a nutraceutical intervention consisting of aspirin and eicosapentaenoic acid. Inflammatory markers and specialized proresolving mediators were measured in serum and the intestinal mucosa of rats, respectively. RESULTS: We observed a significant reduction in quality of recovery scores on postoperative days 1 (median, interquartile: 6 [4.75-8.25] vs naive rats: 17.5 [15.5-18]), 2 (median, interquartile: 13 [11.25-13.25], P < 0.001 vs naive rats: 17 [17-18], P = 0.001), and 3 (median, interquartile: 14.5 [13.5-16] vs naive rats: 17 [15.75-18], P < 0.02). Surgery promoted a significant increase in the concentrations of inflammatory cytokines, but it reduced levels of interleukin-12p70 and macrophage colony-stimulating factor. Lipoxin B4 and 13-HODE were significantly higher in laparotomized rats. Aspirin + eicosapentaenoic acid substantially improved recovery scores and modulated the postsurgical inflammatory response. CONCLUSION: Our novel rat model can be used to study mechanisms governing surgical recovery in rats.