{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:18:40Z","timestamp":1787505520926,"version":"build-2736575974"},"reference-count":45,"publisher":"BMJ","issue":"12","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2015,11,17]]},"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Magnesium exerts analgaesic effects in several animal pain models, as well as in patients affected by acute postoperative pain and neuropathic chronic pain. There is no evidence that magnesium can modulate pain in patients with peripheral arterial occlusive disease (PAOD). We describe the protocol of a single-centre randomised double-blind clinical trial aimed at assessing the efficacy of oral magnesium supplementation in controlling severe pain in patients with advanced PAOD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Adult patients affected by PAOD at stages III and IV of L\u00e8riche-Fontaine classification, who are opioid-na\u00efve, and who have been admitted to our Acute Pain Service for intractable pain, will be eligible. Patients will be randomised to the control group, treated with standard therapy (oxycodone and pregabalin) plus placebo for 2\u2005weeks, or to the experimental group (standard therapy plus magnesium oxide). Patients will be evaluated on days 0, 2, 4, 6, 8, 12 and 14; the following information will being collected: daily oxycodone dose; average and maximum pain (Numerical Rating Scale); pain relief (Pain Relief Scale); characteristics of the pain (Neuropathic Pain Scale); impact of pain on the patient's daily activities (Brief Pain Inventory). The primary outcome will be oxycodone dosage needed to achieve satisfactory analgaesia on day 14. Secondary outcomes will be pain relief on day 2, time needed to achieve satisfactory analgaesia and time needed to achieve a pain reduction of 50%. A sample size calculation was performed for the primary outcome, which estimated a required sample size of 150 patients (75 per group).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval of the study protocol has been obtained from Comitato Etico Provinciale di Brescia, Brescia, Italy. Trial results will be disseminated through scientific journal manuscripts and scientific conference presentations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NCT02455726.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2015-009137","type":"journal-article","created":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T22:29:43Z","timestamp":1450304983000},"page":"e009137","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["MAGnesium-oral supplementation to reduce PAin in patients with severe PERipheral arterial occlusive disease: the MAG-PAPER randomised clinical trial protocol"],"prefix":"10.1136","volume":"5","author":[{"given":"Monica Aida","family":"Venturini","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Critical Care Medicine and Emergency, University of Brescia at Spedali Civili, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Zappa","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care Medicine and Emergency, University of Brescia at Spedali Civili, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosetta","family":"Minelli","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bonardelli","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Brescia at Spedali Civili, Brescia, Italy"},{"name":"Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Lamberti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Bisighini","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zangrandi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Turin","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Rizzolo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Latronico","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care Medicine and Emergency, University of Brescia at Spedali Civili, Brescia, Italy"},{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2015,12,16]]},"reference":[{"key":"2025101810211236000_5.12.e009137.1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(84)90572-6"},{"key":"2025101810211236000_5.12.e009137.2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s00213-005-2200-z","article-title":"Ionotropic and metabotropic glutamate receptor structure and pharmacology","volume":"179","author":"Kew","year":"2005","journal-title":"Psycopharmacology"},{"key":"2025101810211236000_5.12.e009137.3","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1053\/j.trap.2010.04.001","article-title":"Peripheral N-methyl-D-aspartate receptors as possible targets for chronic pain treatment","volume":"14","author":"Recio-Pinto","year":"2010","journal-title":"Techn Reg Anesth Pain Manag"},{"key":"2025101810211236000_5.12.e009137.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0885-3924(00)00213-X"},{"key":"2025101810211236000_5.12.e009137.5","doi-asserted-by":"publisher","DOI":"10.1097\/00002508-200003000-00011"},{"key":"2025101810211236000_5.12.e009137.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpa.2006.12.006"},{"key":"2025101810211236000_5.12.e009137.7","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000081061.12235.55"},{"key":"2025101810211236000_5.12.e009137.8","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1684\/mrh.2011.0296","article-title":"Magnesium involvement in pain","volume":"24","author":"Nechifor","year":"2011","journal-title":"Magnes Res"},{"key":"2025101810211236000_5.12.e009137.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2005.12.004"},{"key":"2025101810211236000_5.12.e009137.10","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.197004"},{"key":"2025101810211236000_5.12.e009137.11","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200203000-00019"},{"key":"2025101810211236000_5.12.e009137.12","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/S1734-1140(09)70172-0","article-title":"Magnesium ions and opioid agonists in vincristine-induced neuropathy","volume":"61","author":"Bujalska","year":"2009","journal-title":"Pharmacol Rep"},{"key":"2025101810211236000_5.12.e009137.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)02618-5"},{"key":"2025101810211236000_5.12.e009137.14","doi-asserted-by":"publisher","DOI":"10.1177\/147323000903700609"},{"key":"2025101810211236000_5.12.e009137.15","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/ael176"},{"key":"2025101810211236000_5.12.e009137.16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00266-006-0194-5","article-title":"Magnesium sulphate as an adjuvant to total intravenous anesthesia in septorhinoplasty: a randomized controlled study","volume":"31","author":"Cizmeci","year":"2007","journal-title":"Aesth Plast Surg"},{"key":"2025101810211236000_5.12.e009137.17","doi-asserted-by":"crossref","first-page":"S163","DOI":"10.1684\/mrh.2009.0177","article-title":"Magnesium in major depression","volume":"22","author":"Nechifor","year":"2009","journal-title":"Magnes Res"},{"key":"2025101810211236000_5.12.e009137.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2013.02.015"},{"key":"2025101810211236000_5.12.e009137.19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1365-2044.2012.07335.x","article-title":"Peri-operative intravenous administration of magnesium sulphate and postoperative pain: a meta-analysis","volume":"68","author":"Albrecht","year":"2013","journal-title":"Anaesthesia"},{"key":"2025101810211236000_5.12.e009137.20","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aei291"},{"key":"2025101810211236000_5.12.e009137.21","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aem407"},{"key":"2025101810211236000_5.12.e009137.22","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199602000-00011"},{"key":"2025101810211236000_5.12.e009137.23","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e31821d72bc"},{"key":"2025101810211236000_5.12.e009137.24","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1007\/s00405-014-3219-8","article-title":"Analgesic effect of magnesium in post-tonsillectomy patients: a prospective randomised clinical trial","volume":"272","author":"Tugrul","year":"2015","journal-title":"Eur Arch Otorhinolatyngol"},{"key":"2025101810211236000_5.12.e009137.25","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/ALN.0b013e3182639d5f","article-title":"Oral magnesium lozenge reduces postoperative sore throat: a randomized, prospective, placebo-controlled study","volume":"117","author":"Borazan","year":"2012","journal-title":"Anesthesiology"},{"key":"2025101810211236000_5.12.e009137.26","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/89.5.711"},{"key":"2025101810211236000_5.12.e009137.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0885-3924(99)00135-9"},{"key":"2025101810211236000_5.12.e009137.28","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1213\/01.ANE.0000057140.33744.65","article-title":"Large-dose intravenous methotrexate-induced cutaneous toxicity: can oral magnesium oxide reduce pain?","volume":"96","author":"Suresh","year":"2003","journal-title":"Anesth Analg"},{"key":"2025101810211236000_5.12.e009137.29","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1213\/00000539-200004000-00025","article-title":"Magnesium sulfate potentiates morphine antinociceptoin at the spinal level","volume":"90","author":"Kroin","year":"2000","journal-title":"Anesth Analg"},{"key":"2025101810211236000_5.12.e009137.30","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/anae.12107","article-title":"A double-blinded randomized controlled study of the value of sequential intravenous and oral magnesium therapy in patients with chronic low back pain with a neuropathic component","volume":"68","author":"Yousef","year":"2013","journal-title":"Anaesthesia"},{"key":"2025101810211236000_5.12.e009137.31","doi-asserted-by":"publisher","DOI":"10.1213\/01.ane.0000261250.59984.cd"},{"key":"2025101810211236000_5.12.e009137.32","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1684\/mrh.2011.0282","article-title":"Oral magnesium treatment in patients with neuropathic pain: a randomized clinical trial","volume":"24","author":"Pickering","year":"2011","journal-title":"Magnes Res"},{"key":"2025101810211236000_5.12.e009137.33","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(95)00113-1"},{"key":"2025101810211236000_5.12.e009137.34","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/86.6.871"},{"key":"2025101810211236000_5.12.e009137.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.03.027"},{"key":"2025101810211236000_5.12.e009137.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(02)03297-6"},{"key":"2025101810211236000_5.12.e009137.37","first-page":"463","article-title":"Long-term results of restorative arterial surgery in obstructive diseases of the arteries","volume":"5","author":"Fontaine","year":"1964","journal-title":"J Cardiovasc Surg"},{"key":"2025101810211236000_5.12.e009137.38","doi-asserted-by":"publisher","DOI":"10.1016\/S0885-3924(01)00409-2"},{"key":"2025101810211236000_5.12.e009137.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2011.04.008"},{"key":"2025101810211236000_5.12.e009137.40","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.2.332"},{"key":"2025101810211236000_5.12.e009137.41","first-page":"841","article-title":"Scala del Dolore Neuropatico, versione italiana di The Neuropathic Pain Scale","volume":"66","author":"Bonezzi","year":"2000","journal-title":"Minerva Anestesiol"},{"key":"2025101810211236000_5.12.e009137.42","first-page":"95","article-title":"Validation if Italian version of the Neuropathic Pain Scale and its clinical implications","volume":"68","author":"Negri","year":"2002","journal-title":"Minerva Anestesiol"},{"key":"2025101810211236000_5.12.e009137.43","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(87)90171-8"},{"key":"2025101810211236000_5.12.e009137.44","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(94)90129-5"},{"key":"2025101810211236000_5.12.e009137.45","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.36076\/ppj.2008\/11\/S105","article-title":"Opioid complications and side effects","volume":"11","author":"Benyamin","year":"2008","journal-title":"Pain Physician"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2015-009137","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T17:21:19Z","timestamp":1760808079000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2015-009137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12,16]]},"published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1136\/bmjopen-2015-009137"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2015-009137","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]}}}