• Didier Bouhassira, Serge Perrot, Thibault Riant, Gaelle Martiné-Fabre, Gisèle Pickering, Caroline Maindet, Nadine Attal, Ranque Garnier Stéphanie S Aix-Marseille University, CNRS, Ecole Centrale Marseille, UMR 7249, Institut Fresnel, Marseille, France. , Jean-Paul Nguyen, Emmanuelle Kuhn, Eric Viel, Patrick Kieffert, Thomas Tölle, Claire Delorme, Rodrigue Deleens, Patrick Giniès, Virginie Corand-Dousset, Clémence Dal-Col, Alain Serrie, Emmanuel Chevrillon, Christian Gov, Juan Fernando Ramirez-Gil, Cécile Delval, Manuella Schaller, Baptiste Bessière, Patrick Houéto, Claudia Sommer, and ProtoTOP group.
• Inserm U987, APHP, CHU Ambroise Paré, UVSQ, Paris-Saclay, Boulogne-Billancourt, France.
• Pain. 2021 Apr 1; 162 (4): 1104-1115.

AbstractNitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia and for short-duration analgesia in various clinical settings mostly in the form of an N2O/O2 50%-50% equimolar mixture (EMONO). Experimental studies have suggested that EMONO could also induce long-lasting analgesic effects related to the blockade of N-methyl-D-aspartate receptors. We designed the first international multicenter proof of concept randomized, placebo-controlled study to assess the efficacy and safety of a 1-hour administration of EMONO or placebo (medical air) on 3 consecutive days up to 1 month after the last administration in patients with chronic peripheral neuropathic pain. A total of 240 patients were recruited in 22 centers in France and Germany and randomly assigned to 1 study group (120 per group). Average pain intensity (primary outcome), neuropathic pain characteristics (Neuropathic Pain Symptom Inventory), Patient Global Impression of Change, anxiety, depression, and quality of life were systematically assessed before and after treatment. The changes in average pain intensity between baseline and 7 days after the last administration were not significantly different between the 2 groups. However, evoked pain intensity (predefined secondary endpoint) and Patient Global Impression of Change (exploratory endpoint) were significantly improved in the EMONO group, and these effects were maintained up to 4 weeks after the last treatment administration. Mostly transient side effects were reported during the treatment administration. These encouraging results provide a basis for further investigation of the long-term analgesic effects of EMONO in patients with neuropathic pain.Copyright © 2020 International Association for the Study of Pain.

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