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In recent years, GLP-1 role in neuronal pathways has expanded its therapeutic potential. We aim to comprehensively evaluate the relevance of GLP-1 in headache and pain disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature search was conducted on PubMed and Embase (Ovid) databases using the search terms \u201cGLP-1\u201d and \u201cpain\u201d. Animal and human studies published in English language were included. Abstracts, reviews, and articles on other disorders than \u201cpain\u201d were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The search strategy identified 833 hits, of which 42 studies were included in the final review. The studies were categorized into four groups: inflammatory pain and osteoarthritis, headaches, neuropathic pain and diabetic neuropathy, and visceral pain and irritable bowel syndrome. GLP-1 receptor (GLP-1R) agonists, like liraglutide, have shown analgesic effects by modulating pain hypersensitivity in animal models of inflammatory and neuropathic pain. GLP-1 is involved in migraine mechanisms and GLP-1R agonists are beneficial in individuals with idiopathic intracranial hypertension. Additionally, GLP-1R agonists reduce visceral hypersensitivity and ameliorate symptoms in patients with irritable bowel syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The therapeutic scope of GLP-1R agonists is expanding beyond traditional metabolic targets, highlighting its potential for headache and pain disorders. Engineering bimodal molecules that integrate GLP-1R agonism with specific pain-related mechanisms may offer innovative therapeutic options.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10194-024-01821-3","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T07:02:41Z","timestamp":1720767761000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Glucagon-like peptide-1 (GLP-1) receptor agonists for headache and pain disorders: a systematic review"],"prefix":"10.1186","volume":"25","author":[{"given":"Wael","family":"Halloum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef Al","family":"Dughem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Beier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanfranco","family":"Pellesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"issue":"2","key":"1821_CR1","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/s42255-020-00327-x","volume":"3","author":"FM Gribble","year":"2021","unstructured":"Gribble FM, Reimann F (2021) Metabolic messengers: glucagon-like peptide 1. 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