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

Pellesi, Lanfranco; Chaudhry, Basit Ali; Vollesen, Anne Luise Haulund; Snoer, Agneta; Baumann, K.; Skov, Per Stahl; Jensen, Rigmor Højland

doi:10.1177/03331024211056248

Cited by 17 publications

(16 citation statements)

References 37 publications

(59 reference statements)

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“…One explanation as to why CGRP-mAbs have not worked as well in CH as they have in migraine may lie in the attack mechanism. Up to 30% of migraine attacks may be CGRP-independent (95) and similar non-CGRP mechanisms may be at play in CH, as attacks triggered by infusion of vasoactive intestinal peptide or pituitary adenylate cyclase-activating polypeptide-38 did not lead to increased levels of CGRP (96). Indeed, the data using CGRP as a pharmacological trigger gave a success rate of 89% in eCH patients during their active period (cluster bout) and only 50% in cCH patients (87).…”

Section: Preventive Pharmacological Treatmentsmentioning

confidence: 99%

Management of cluster headache: Treatments and their mechanisms

Peng,

Burish

2023

Cephalalgia

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Background The management of cluster headache is similar to that of other primary headache disorders and can be broadly divided into acute and preventive treatments. Acute treatments for cluster headache are primarily delivered via rapid, non-oral routes (such as inhalation, nasal, or subcutaneous) while preventives include a variety of unrelated treatments such as corticosteroids, verapamil, and galcanezumab. Neuromodulation is becoming an increasingly popular option, both non-invasively such as vagus nerve stimulation when medical treatment is contraindicated or side effects are intolerable, and invasively such as occipital nerve stimulation when medical treatment is ineffective. Clinically, this collection of treatment types provides a range of options for the informed clinician. Scientifically, this collection provides important insights into disease mechanisms. Methods Two authors performed independent narrative reviews of the literature on guideline recommendations, clinical trials, real-world data, and mechanistic studies. Results Cluster headache is treated with acute treatments, bridge treatments, and preventive treatments. Common first-line treatments include subcutaneous sumatriptan and high-flow oxygen as acute treatments, corticosteroids (oral or suboccipital injections) as bridge treatments, and verapamil as a preventive treatment. Some newer acute (non-invasive vagus nerve stimulation) and preventive (galcanezumab) treatments have excellent clinical trial data for episodic cluster headache, while other newer treatments (occipital nerve stimulation) have been specifically tested in treatment-refractory chronic cluster headache. Most treatments are suspected to act on the trigeminovascular system, the autonomic system, or the hypothalamus. Conclusions The first-line treatments have not changed in recent years, but new treatments have provided additional options for patients.

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Section: Preventive Pharmacological Treatmentsmentioning

confidence: 99%

Management of cluster headache: Treatments and their mechanisms

Peng,

Burish

2023

Cephalalgia

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“…The relation between CH and vasoactive peptides was explored in 11 studies. 22,[25][26][27][28][29][30][31][32][33][34] They were carried out between 1994 and 2022…”

Section: Vasoactive Peptidesmentioning

confidence: 99%

“…The remaining studies focusing on CGRP examined potential differences within the CH states with inconsistent results. Four studies demonstrated increased CGRP levels in eCHb compared to eCHr and cCH,22,26,31,35 while two27,29 did not detect significant differences among the three disease states.…”

mentioning

confidence: 90%

Biomarkers in cluster headache: A systematic review

Søborg,

Jensen,

Barloese

et al. 2023

Headache

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ObjectiveTo systematically investigate previously examined biomarkers in blood, urine, cerebrospinal fluid, tear fluid, and saliva of patients with cluster headache.BackgroundCluster headache is a condition with extensive clinical challenges in terms of diagnosis and treatment. Identification of a biomarker with diagnostic implications or as a potential treatment target is highly warranted.MethodsWe conducted a systematic review including peer reviewed full text of studies that measured biochemical compounds in either blood, urine, cerebrospinal fluid, tear fluid, or saliva of patients with cluster headache diagnosed after the implementation of the International Classification of Headache Disorders (1988) written in English, Danish, Swedish, or Norwegian. Inclusion required a minimum of five participants. The search was conducted in PubMed and EMBASE, in September 2022, and extracted data were screened by two authors. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines for reporting systematic reviews were followed. The Newcastle–Ottawa Scale was used to assess the risk of bias in case–controlled studies.ResultsWe included 40 studies involving 832 patients with cluster headache and 872 controls, evaluating 80 potential biomarkers. The risk of bias for case–controlled studies was a median of 6 (range: 3–8) and 20 studies out of 40 (50%) were of fair or good quality. Most studies were identified within three groups: hypothalamic‐regulated hormones, inflammatory markers, and neuropeptides. Among the hypothalamic hormones, cortisol was the most frequently investigated (N = 7) and was elevated in cluster headache in most of the studies. The most frequently examined inflammatory marker was interleukin 1 (N = 3), but findings were divergent. Calcitonin gene–related peptide was the most investigated neuropeptide (N = 9) and all studies found increased levels during attacks.ConclusionBiomarker findings have been inconsistent and widely non‐specific for cluster headache, which explains why none of the previous studies succeeded in identifying a unique biomarker for cluster headache, but instead contributed to substantiating the underlying pathophysiologic mechanisms. Several of the examined biomarkers could hold promise as markers for disease activity but are unfit for a clear distinction from both controls and other headaches.

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“…Concentrations of plasma CGRP were determined by radioimmunoassay using antibody AB 4-2905 and α-CGRP as calibrator (13), as previously described (14,15).…”

Section: Plasma Cgrpmentioning

confidence: 99%

Plasma Levels of CGRP During a 2-h Infusion of VIP in Healthy Volunteers and Patients With Migraine: An Exploratory Study

et al. 2022

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IntroductionThe activation of perivascular fibers and the consequent release of vasoactive peptides, including the vasoactive intestinal polypeptide (VIP), play a role in migraine pathogenesis. A 2-h infusion of VIP provoked migraine, but the mechanisms remain unknown. We investigated whether 2-h infusion of VIP caused alterations in plasma levels of the calcitonin gene-related peptide (CGRP) and whether any changes might be related to the induced migraine attacks.Materials and MethodsWe enrolled individuals with episodic migraine without aura and healthy participants to randomly receive a 2-h infusion of either VIP (8 pmol/kg/min) or placebo (sterile saline) in two randomized, placebo-controlled crossover trials. We collected clinical data and measured plasma levels of VIP and CGRP at fixed time points: at baseline (T0) and every 30 min until 180 min (T180) after the start of the infusion.ResultsBlood samples were collected from patients with migraine (n = 19) and healthy individuals (n = 12). During VIP infusion, mixed effects analysis revealed a significant increase in plasma CGRP (p = 0.027) at T30 (vs. T180, adjusted p-value = 0.039) and T60 (vs. T180, adjusted p-value = 0.027) in patients with migraine. We found no increase in plasma CGRP during VIP-induced migraine attacks (p = 0.219). In healthy individuals, there was no increase in plasma CGRP during VIP (p = 0.205) or placebo (p = 0.428) days.DiscussionPlasma CGRP was elevated in patients with migraine during a prolonged infusion of VIP, but these alterations were not associated with VIP-induced migraine attacks. Given the exploratory design of our study, further investigations are needed to clarify the role of CGRP in VIP-induced migraine.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03989817 and NCT04260035.

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

Cited by 17 publications

References 37 publications

Management of cluster headache: Treatments and their mechanisms

Management of cluster headache: Treatments and their mechanisms

Biomarkers in cluster headache: A systematic review

Plasma Levels of CGRP During a 2-h Infusion of VIP in Healthy Volunteers and Patients With Migraine: An Exploratory Study

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