{"doi":"10.1177/0333102420981666","title":"Hypersensitivity to calcitonin gene-related peptide in chronic migraine","abstract":"<jats:sec>\n                    <jats:title>Objective</jats:title>\n                    <jats:p>To investigate if calcitonin gene-related peptide infusion induces migraine-like attacks in chronic migraine patients.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>Fifty-eight patients with chronic migraine, either with or without headache on the experimental day, were assessed for the incidence of migraine-like attacks after an intravenous infusion with calcitonin gene-related peptide 1.5 µg/min over 20 min. The primary endpoint was the incidence of migraine-like attacks after calcitonin gene-related peptide. Exploratory endpoints were the association between the incidence of migraine-like attacks and presence of headache on the experimental day, and headache frequency in the past month. Migraine-like attack data was compared to a historic cohort of 91 episodic migraine patients without headache on the experimental day. Total tenderness score, pressure-pain threshold and supra-threshold pressure pain at baseline were investigated in relation to incidence of migraine-like attacks and presence of headache on the experimental day.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>In total, 83% of the 58 chronic migraine patients developed migraine-like attacks after calcitonin gene-related peptide infusion. Migraine-like attacks were found in 92% of chronic migraine patients with headache on the experimental day compared to 65% of chronic migraine patients without headache on the experimental day ( p = 0.035). No differences were observed in total tenderness score and pressure-pain threshold between chronic migraine patients with and without headache on the experimental day. The incidence of migraine-like attacks following calcitonin gene-related peptide in chronic migraine patients without headache (65%) was equal to the historic cohort of 91 episodic migraine patients without headache (67%) on the experimental day.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions</jats:title>\n                    <jats:p>Chronic migraine patients are hypersensitive to calcitonin gene-related peptide. The potency of calcitonin gene-related peptide as a migraine inductor is increased in chronic migraine patients with ongoing headache. We suggest that calcitonin gene-related peptide, besides being a migraine trigger also acts as a modulator of nociceptive transmission in the trigeminal system.</jats:p>\n                  </jats:sec>","journal":"Cephalalgia","year":2021,"id":645921,"datarank":0.5495342469194471,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.0,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":284818,"name":"Håkan Ashina","orcid":"0000-0002-6268-727X","position":1,"is_corresponding":false},{"id":1682101,"name":"Zixuan Alice Zhuang","orcid":null,"position":2,"is_corresponding":false},{"id":1682102,"name":"Cristina Lopez Lopez","orcid":null,"position":3,"is_corresponding":false},{"id":1682103,"name":"Josefin Snellman","orcid":null,"position":4,"is_corresponding":false},{"id":210926,"name":"Messoud Ashina","orcid":null,"position":5,"is_corresponding":false},{"id":339340,"name":"Henrik Winther Schytz","orcid":"0000-0002-6262-2986","position":6,"is_corresponding":false},{"id":339337,"name":"Afrim Iljazi","orcid":"0000-0002-4190-3834","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Hypersensitivity to calcitonin gene-related peptide in chronic migraine","abstract":"<jats:sec>\n                    <jats:title>Objective</jats:title>\n                    <jats:p>To investigate if calcitonin gene-related peptide infusion induces migraine-like attacks in chronic migraine patients.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>Fifty-eight patients with chronic migraine, either with or without headache on the experimental day, were assessed for the incidence of migraine-like attacks after an intravenous infusion with calcitonin gene-related peptide 1.5 µg/min over 20 min. The primary endpoint was the incidence of migraine-like attacks after calcitonin gene-related peptide. Exploratory endpoints were the association between the incidence of migraine-like attacks and presence of headache on the experimental day, and headache frequency in the past month. Migraine-like attack data was compared to a historic cohort of 91 episodic migraine patients without headache on the experimental day. Total tenderness score, pressure-pain threshold and supra-threshold pressure pain at baseline were investigated in relation to incidence of migraine-like attacks and presence of headache on the experimental day.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>In total, 83% of the 58 chronic migraine patients developed migraine-like attacks after calcitonin gene-related peptide infusion. Migraine-like attacks were found in 92% of chronic migraine patients with headache on the experimental day compared to 65% of chronic migraine patients without headache on the experimental day ( p = 0.035). No differences were observed in total tenderness score and pressure-pain threshold between chronic migraine patients with and without headache on the experimental day. The incidence of migraine-like attacks following calcitonin gene-related peptide in chronic migraine patients without headache (65%) was equal to the historic cohort of 91 episodic migraine patients without headache (67%) on the experimental day.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions</jats:title>\n                    <jats:p>Chronic migraine patients are hypersensitive to calcitonin gene-related peptide. The potency of calcitonin gene-related peptide as a migraine inductor is increased in chronic migraine patients with ongoing headache. We suggest that calcitonin gene-related peptide, besides being a migraine trigger also acts as a modulator of nociceptive transmission in the trigeminal system.</jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33322922","pmcid":null,"openalex_id":"https://openalex.org/W3111709648","authors":[],"funders":[{"funder_name":"Novartis Pharma","grant_id":"","title":null}],"total_grants":1,"fwci":2.547,"citation_percentile":0.90853432,"influential_citations":0,"citation_trend":[{"year":2021,"count":3},{"year":2022,"count":7},{"year":2023,"count":8},{"year":2024,"count":18},{"year":2025,"count":2}],"oa_status":"closed","license":"https://journals.sagepub.com/page/policies/text-and-data-mining-license","oa_locations":[{"url":"https://journals.sagepub.com/doi/pdf/10.1177/0333102420981666","host_type":"publisher"},{"url":"https://journals.sagepub.com/doi/full-xml/10.1177/0333102420981666","host_type":"publisher"},{"url":"https://doi.org/10.1177/0333102420981666","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33322922","host_type":"repository"},{"url":"https://researchprofiles.ku.dk/da/publications/9079a5d1-dd32-4c71-ab9a-3b894b9a69ad","host_type":"repository"}],"fields_of_study":["Migraine and Headache Studies","Pain Management and Opioid Use","Traumatic Brain Injury and Neurovascular Disturbances","Adult","Aged","Calcitonin Gene-Related Peptide","Female","Headache","Humans","Hypersensitivity","Incidence","Infusions, Intravenous","Male","Middle Aged","Migraine Disorders"],"mesh_terms":["Adult","Aged","Female","Headache","Humans","Hypersensitivity","Infusions, Intravenous","Male","Middle Aged","Migraine Disorders","Calcitonin Gene-Related Peptide","Incidence"],"keywords":["Calcitonin gene-related peptide","Medicine","Migraine","Calcitonin","Gene","Migraine Disorders","Peptide","Genetics","Endocrinology","Internal medicine","Neuropeptide","Receptor","Biology","Biochemistry","Susceptibility","Pathophysiology","Central Sensitisation","Peripheral Sensitisation","Human Migraine Models"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T10:39:40.680432Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}