{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:51:13Z","timestamp":1788501073889,"version":"build-2803163510"},"reference-count":19,"publisher":"BMJ","issue":"8","funder":[{"name":"NIH","award":["K08CA228039"],"award-info":[{"award-number":["K08CA228039"]}]},{"DOI":"10.13039\/100010976","name":"Reflex Sympathetic Dystrophy Syndrome Association","doi-asserted-by":"publisher","award":["Study was supported by a research grant from Refle"],"award-info":[{"award-number":["Study was supported by a research grant from Refle"]}],"id":[{"id":"10.13039\/100010976","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cleveland Clinic Catalyst","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2023,10,2]]},"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with a diagnosis of CRPS were randomized to either 2\u2009hours 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\u2009week and 1\u2009month. Secondary and exploratory outcomes were physical and mental health (PRMOIS-29 v2 survey), specific neuropathic pain symptoms (McGill short-form questionnaire), and opioid consumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2212Air-Oxygen) of \u22120.57 (95% CI: \u22121.42 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\u2212Air-Oxygen) of 0.13 (95% CI: \u22120.16 to 0.43), mental health 0.087 (95% CI: \u22120.31 to 0.48), and Patient Global Impression of Change score \u22120.7 (95% CI: \u22121.85 to 0.46).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Compared with air\/oxygen, 2\u2009hours 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rapm-2023-104537","type":"journal-article","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T12:50:12Z","timestamp":1698497412000},"page":"573-580","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Nitrous oxide for the treatment of complex regional pain syndrome: a randomized blinded trial"],"prefix":"10.1136","volume":"49","clinical-trial-number":[{"clinical-trial-number":"nct03879538","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Jason","family":"Hale","sequence":"first","affiliation":[{"name":"Department of Pain Management, Cleveland Clinic, Cleveland, Ohio, 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Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2414-0951","authenticated-orcid":false,"given":"Orkun","family":"Kopac","sequence":"additional","affiliation":[{"name":"Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio, USA"},{"name":"Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-0762","authenticated-orcid":false,"given":"Ece","family":"Yamak Altinpulluk","sequence":"additional","affiliation":[{"name":"Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozkan","family":"Onal","sequence":"additional","affiliation":[{"name":"Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio, USA"},{"name":"Department of Anesthesiology 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