Agneta Snoer1, Anne Luise H Vollesen1, Rasmus P Beske1, Song Guo1, Jan Hoffmann2, Jan Fahrenkrug3, Niklas Rye Jørgensen4,5, Torben Martinussen6, Rigmor H Jensen1, Messoud Ashina1. 1. 1 Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 2. 2 Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 3. 3 Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. 4. 4 Department of Clinical Biochemistry, Rigshospitalet Glostrup, Glostrup, Denmark. 5. 5 OPEN, Odense Patient Data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. 6. 6 Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
Abstract
OBJECTIVE: To investigate the role of calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide in cluster headache, we measured these vasoactive peptides interictally and during experimentally induced cluster headache attacks. METHODS: We included patients with episodic cluster headache in an active phase (n = 9), episodic cluster headache patients in remission (n = 9) and patients with chronic cluster headache (n = 13). Cluster headache attacks were induced by infusion of calcitonin gene-related peptide (1.5 µg/min) in a randomized, double-blind, placebo controlled, two-way cross-over study. At baseline, we collected interictal blood samples from all patients and during 11 calcitonin gene-related peptide-induced cluster headache attacks. RESULTS: At baseline, episodic cluster headache patients in remission had higher plasma levels of calcitonin gene-related peptide, 100.6 ± 36.3 pmol/l, compared to chronic cluster headache patients, 65.9 ± 30.5 pmol/l, ( p = 0.011). Episodic cluster headache patients in active phase had higher PACAP38 levels, 4.0 ± 0.8 pmol/l, compared to chronic cluster headache patients, 3.3 ± 0.7 pmol/l, ( p = 0.033). Baseline levels of vasoactive intestinal polypeptide did not differ between cluster headache groups. We found no attack-related increase in calcitonin gene-related peptide, PACAP38 or vasoactive intestinal polypeptide levels during calcitonin gene-related peptide-induced cluster headache attacks. CONCLUSIONS: This study suggests that cluster headache disease activity is associated with alterations of calcitonin gene-related peptide expression. Future studies should investigate the potential of using calcitonin gene-related peptide measurements in monitoring of disease state and predicting response to preventive treatments, including response to anti-calcitonin gene-related peptide monoclonal antibodies.
RCT Entities:
OBJECTIVE: To investigate the role of calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide in cluster headache, we measured these vasoactive peptides interictally and during experimentally induced cluster headache attacks. METHODS: We included patients with episodic cluster headache in an active phase (n = 9), episodic cluster headachepatients in remission (n = 9) and patients with chronic cluster headache (n = 13). Cluster headache attacks were induced by infusion of calcitonin gene-related peptide (1.5 µg/min) in a randomized, double-blind, placebo controlled, two-way cross-over study. At baseline, we collected interictal blood samples from all patients and during 11 calcitonin gene-related peptide-induced cluster headache attacks. RESULTS: At baseline, episodic cluster headachepatients in remission had higher plasma levels of calcitonin gene-related peptide, 100.6 ± 36.3 pmol/l, compared to chronic cluster headachepatients, 65.9 ± 30.5 pmol/l, ( p = 0.011). Episodic cluster headachepatients in active phase had higher PACAP38 levels, 4.0 ± 0.8 pmol/l, compared to chronic cluster headachepatients, 3.3 ± 0.7 pmol/l, ( p = 0.033). Baseline levels of vasoactive intestinal polypeptide did not differ between cluster headache groups. We found no attack-related increase in calcitonin gene-related peptide, PACAP38 or vasoactive intestinal polypeptide levels during calcitonin gene-related peptide-induced cluster headache attacks. CONCLUSIONS: This study suggests that cluster headache disease activity is associated with alterations of calcitonin gene-related peptide expression. Future studies should investigate the potential of using calcitonin gene-related peptide measurements in monitoring of disease state and predicting response to preventive treatments, including response to anti-calcitonin gene-related peptide monoclonal antibodies.