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Patients with CLTI often experience chronic pain that significantly impairs their quality of life. The pain experienced by patients with CLTI can be complex and challenging to manage, requiring a refined approach to balance analgesic efficacy with potential adverse pharmacological effects and pre-existing, competing comorbidities. This systematic review protocol aims to explore, critically assess and compare the effectiveness and safety of different pharmacological and locoregional analgesic approaches for managing pain occurring secondary to CLTI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The methods will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Five electronic databases will be searched. At least two reviewers will perform study screening, data extraction and quality assessments. Any disagreements will be arbitrated by an additional independent reviewer. Randomised studies, observational cohort studies and case series consisting of four or more patients will be included. Grey literature will be excluded. The primary outcome will be the effectiveness of analgesia. Secondary outcomes will include adverse effects of analgesia and functional outcomes. Where the data allow, appropriate quantitative synthesis methods will be pursued.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This systematic review will not involve primary data collection; thus, no ethical approval is required. The results will be disseminated in a peer-reviewed publication and presented at conferences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42024561800<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-090678","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T09:10:32Z","timestamp":1752657032000},"page":"e090678","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring optimal analgesic strategies for chronic limb-threatening ischaemia: a systematic review protocol"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4959-0235","authenticated-orcid":false,"given":"Thanapon","family":"Ekkunagul","sequence":"first","affiliation":[{"name":"Epidemiology Group, University of Aberdeen Institute of 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