Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack

Pain ◽  
1995 ◽  
Vol 60 (2) ◽  
pp. 119-123 ◽  
Author(s):  
Marcello Fanciullacci ◽  
Massimo Alessandri ◽  
Michela Figini ◽  
Pierangelo Geppetti ◽  
Sergio Michelacci
Keyword(s):  
Cluster Headache ◽  
Calcitonin Gene Related Peptide ◽  
Headache Attack ◽  
Related Peptide ◽  
Cluster Headache Attack ◽  
Calcitonin Gene

Sensory Neuropeptides (Substance P, Calcitonin Gene-Related Peptide) and Vasoactive Intestinal Polypeptide in Human Saliva: Their Pattern in Migraine and Cluster Headache

Cephalalgia ◽  
1990 ◽  
Vol 10 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Maria Nicolodi ◽  
Elena Del Bianco
Keyword(s):  
Substance P ◽  
Cluster Headache ◽  
Vasoactive Intestinal Polypeptide ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Control Subjects ◽  
Cluster Headache Attack ◽  
Calcitonin Gene ◽  
Symptomatic Side ◽  
Intestinal Polypeptide

Substance P, calcitonin gene-related peptide and vasoactive intestinal polypeptide-like immunoreactivities have been evaluated in the saliva of 15 subjects suffering from migraine without aura and 16 control subjects. All three peptides were also measured in the symptomatic/non-symptomatic side saliva sampled from 10 cluster headache sufferers during the cluster period, 5 cluster headache sufferers out of the cluster period, as well as in the right and left side saliva of 18 control subjects. The most interesting result gives a clear difference in common migraine and cluster headache salivary vasoactive intestinal polypeptide-like immunoreactivity contents. In fact, these are enhanced during cluster headache attack and decreased during migraine attack when compared with the interictal period vasoactive intestinal polypeptide-like immunoreactivity levels. Another remarkable finding concerns the significant increase of substance P-like immunoreactivity and calcitonin gene-related peptide-like immunoreactivity levels, from basal values, in the saliva sampled during both migraine and cluster headache attacks. Control subjects showed a calcitonin gene-related peptide-like immunoreactivity and substance P-like immunoreactivity salivary contents significantly higher than migraine sufferers' saliva sampled in basal conditions. Conversely, calcitonin gene-related peptide-like immunoreactivities levels in controls were lower than in cluster headache sufferers' saliva obtained during intervals. Finally, during cluster headache attacks the enhancement of substance P-like immunoreactivity and vasoactive intestinal polypeptide-like immunoreactivity salivary contents interest the non-symptomatic side, whereas the symptomatic side salivary substance P-like immunoreactivity and vasoactive intestinal poly-peptide-like immunoreactivity contents remain unchanged. These findings do not allow any final conclusion. However, this biochemical evaluation indicates relevant changes of the salivary neuropeptides in diseases, such as migraine and cluster headache, in which pain transmission is surely involved.

scholarly journals Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache: Results from a retrospective case series support individual treatment attempts

Cephalalgia ◽  
2020 ◽  
Vol 40 (14) ◽  
pp. 1574-1584 ◽  
Author(s):  
Ruth Ruscheweyh ◽  
Gregor Broessner ◽  
Gudrun Goßrau ◽  
Katja Heinze-Kuhn ◽  
Tim P Jürgens ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Calcitonin Gene Related Peptide ◽  
Chronic Cluster Headache ◽  
Individual Treatment ◽  
Attack Frequency ◽  
Peptide Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Receptor Antibodies ◽  
Headache Patients

Objective To assess the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor in chronic cluster headache (CCH) treatment under real world conditions. Background Calcitonin gene-related peptide has an important pathophysiological role in cluster headache. Although the randomised controlled trial with the calcitonin gene-related peptide antibody galcanezumab was negative, chronic cluster headache patients with insufficient response to other preventive treatments have been receiving individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies. Methods Data from 22 chronic cluster headache patients who received at least one dose of a calcitonin gene-related peptide(-receptor) antibody and recorded attack frequency in a headache diary were retrospectively collected at eight headache centres. Results The number of previous preventive therapies was 6.5 ± 2.4 (mean ± standard deviation, range: 2–11). The average number of attacks per week was 23.3 ± 16.4 at baseline and significantly decreased by −9.2 ± 9.7 in the first month of treatment with a calcitonin gene-related peptide(-receptor) antibody ( p < 0.001). Fifty-five percent of the patients were 50% responders and 36% were 75% responders with respect to attack frequency. Significant reduction of attack frequency started at week 1 (−6.8 ± 2.8 attacks, p < 0.01). Results were corroborated by significant decreases in weekly uses of acute headache medication (−9.8 ± 7.6, p < 0.001) and pain intensity during attacks (−1.2 ± 2.0, numerical rating scale (NRS) [0–10], p < 0.01) in the first month. In months 2 (n = 14) and 3 (n = 10), reduction of attack frequency from baseline was −8.0 ± 8.4 ( p = 0.004) and −9.1 ± 10.0 ( p = 0.024), respectively. Conclusion Under real-world conditions, individual treatment with calcitonin gene-related peptide(-receptor) antibodies was effective in 55% of our chronic cluster headache patients. This finding supports individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies in chronic cluster headache patients insufficiently responding to other therapies.

scholarly journals Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache

2020 ◽  
Vol 10 (1) ◽  
pp. 30 ◽  
Author(s):  
Andrea Carmine Belin ◽  
Caroline Ran ◽  
Lars Edvinsson
Keyword(s):  
Cluster Headache ◽  
Pain Perception ◽  
Primary Headache ◽  
Active Phase ◽  
Calcitonin Gene Related Peptide ◽  
Primary Headaches ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Autonomic Reflex

Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in the intense pain perception and in the associated distinctive vasodilation. So far, clinical tests of CGRP antibodies have been inconclusive in CH patients. This review summarizes the current state of knowledge on the role of CGRP in CH pathology, and as a target for future treatments.

Baseline tear fluid CGRP is elevated in active cluster headache patients as long as they have not taken attack abortive medication

Cephalalgia ◽  
2020 ◽  
pp. 033310242094985
Author(s):  
Katharina Kamm ◽  
Andreas Straube ◽  
Ruth Ruscheweyh
Keyword(s):  
Cluster Headache ◽  
Trigeminal Nerve ◽  
Calcitonin Gene Related Peptide ◽  
Chronic Cluster Headache ◽  
Tear Fluid ◽  
Abortive Medication ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Active Cluster ◽  
Headache Patients

Background Calcitonin gene-related peptide plays a key role in cluster headache pathophysiology. It is released from the trigeminal nerve, which also innervates the eye. In this study, we tested if tear fluid calcitonin gene-related peptide measurement detects elevated calcitonin gene-related peptide levels in cluster headache patients compared to controls. Methods Calcitonin gene-related peptide concentration in tear fluid and plasma of 16 active episodic and 11 chronic cluster headache patients (all outside acute attacks) and 60 controls were assessed using ELISA. Results Cluster headache patients without use of attack abortive medication in the last 48 h showed significantly elevated tear fluid calcitonin gene-related peptide levels (1.78 ± 1.57 ng/ml, n = 17) compared to healthy controls (0.79 ± 0.74 ng/ml, p = 0.003) and compared to cluster headache patients who had used attack abortive medication in the last 48 h (0.84 ± 1.40 ng/ml, n = 10, p = 0.022). High calcitonin gene-related peptide levels in cluster headache patients were independent of the occurrence of a cluster headache attack in the last 48 hours (no attack: 1.95 ± 1.65 ng/ml, n = 8; attack: 1.63 ± 1.59 ng/ml, n = 9, p = 0.82) as long as no acute medication was used. No significant difference in tear fluid calcitonin gene-related peptide levels between episodic (1.48 ± 1.34 ng/ml) and chronic cluster headache patients (2.21 ± 1.88 ng/ml, p = 0.364) was detected. In contrast to these results in tear fluid, there were no significant group differences in plasma calcitonin gene-related peptide levels. Conclusion This study shows that active cluster headache patients have increased calcitonin gene-related peptide levels in tear fluid compared to healthy subjects, which are reduced to control levels after intake of attack abortive medication. Calcitonin gene-related peptide measurement in tear fluid is non-invasive, and has the advantage of allowing direct access to calcitonin gene-related peptide released from the trigeminal nerve.

PACAP38- and VIP-induced cluster headache attacks are not associated with changes of plasma CGRP or markers of mast cell activation

Cephalalgia ◽  
2021 ◽  
pp. 033310242110562
Author(s):  
Lanfranco Pellesi ◽  
Basit Ali Chaudhry ◽  
Anne Luise Haulund Vollesen ◽  
Agneta Henriette Snoer ◽  
Katrine Baumann ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cluster Headache ◽  
Vasoactive Intestinal Polypeptide ◽  
Plasma Levels ◽  
Cell Activation ◽  
Calcitonin Gene Related Peptide ◽  
Mast Cell Activation ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Headache Patients

Background Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide can provoke cluster headache attacks in up to half of cluster headache patients in their active phase. At present, it is unknown whether provoked attacks are mediated via calcitonin gene-related peptide or mast cell activation. Methods All enrolled patients with cluster headache were randomly allocated to receive a continuous infusion of either PACAP38 (10 pmol/kg/min) or vasoactive intestinal polypeptide (8 pmol/kg/min) over 20 min. We collected clinical data and measured plasma levels of calcitonin gene-related peptide and markers of mast cell activation (tryptase and histamine) at fixed time points: at baseline (T0), at the end of the infusion (T20), 10 min after the infusion (T30), and 70 min after the infusion (T90). Results Blood was collected from episodic cluster headache patients in active phase (n = 14), episodic cluster headache patients in remission (n = 15), and chronic cluster headache patients (n = 15). At baseline, plasma levels of calcitonin gene-related peptide, tryptase, and histamine were not different among the three study groups. Plasma levels of calcitonin gene-related peptide ( p = 0.7074), tryptase ( p = 0.6673), or histamine ( p = 0.4792) remained unchanged during provoked attacks compared to attack-free patients. Conclusion Cluster headache attacks provoked by either PACAP38 or vasoactive intestinal polypeptide were not accompanied by alterations of plasma calcitonin gene-related peptide, tryptase or histamine. The provoked attacks may not be mediated by calcitonin gene-related peptide or mast cell activation. Trial Registration: The study is registered at ClinicalTrials.gov (NCT03814226).

scholarly journals Erenumab for chronic cluster headache: A case report

2020 ◽  
Vol 3 ◽  
pp. 251581632094771
Author(s):  
Franz Riederer ◽  
Allyson M Wenner
Keyword(s):  
Cluster Headache ◽  
Preventive Treatment ◽  
Calcitonin Gene Related Peptide ◽  
Chronic Cluster Headache ◽  
Attack Frequency ◽  
Related Peptide ◽  
Episodic Cluster Headache ◽  
Calcitonin Gene ◽  
Repeated Doses ◽  
Randomized Control

The preventive treatment for cluster headache is often limited by a lack of efficacy or side effects. Calcitonin gene-related peptide (CGRP) has been implicated in the pathophysiology of cluster headache. Galcanezumab, a monoclonal antibody against calcitonin gene-related peptide (CGRP), significantly reduced the frequency of episodic cluster headache attacks. We report the case of a 38-year-old woman with chronic refractory cluster headache and comorbid migraine who received erenumab in 4 repeated doses of 70 mg subcutaneously over 25 weeks. Attack frequency decreased from three attacks per day to several attacks per week. Erenumab seemed to be highly effective in the prevention of cluster headache attacks in this patient. We suggest that randomized control trials should be performed.

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