Trial reportBrain : a journal of neurology2023
Second messenger signalling bypasses CGRP receptor blockade to provoke migraine attacks in humans.
Trial report in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Erenumab for Chronic Cluster Headache: A Randomized Clinical Trial.JAMA network open · 2025Trial
- PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial.The journal of headache and pain · 2025Trial
- Acupuncture modulates migraine-related neural and neuroendocrine regulatory pathways.The journal of headache and pain · 2026Review
- Pharmacological mechanisms underlying neurovascular alterations related to resistant and refractory migraine: CGRP pathways and beyond.The journal of headache and pain · 2026Review
- Altered static-dynamic interhemispheric connectivity and transcriptional features underlying lateralization in patients with migraine.The journal of headache and pain · 2026Article
- Emerging pharmacological targets in migraine therapy: CGRP and beyond.Frontiers in pharmacology · 2026Review
- Article
- The vessel-to-neuron trigeminovascular hypothesis of migraine pathogenesis - the 'pro' argument.The journal of headache and pain · 2025Review
- Possible Role of Novel Mitochondrial Subsets in Migraine.Life (Basel, Switzerland) · 2025Review
- Calcitonin gene-related peptide in newly diagnosed idiopathic intracranial hypertension: a prospective, cross-sectional, case-control study of cerebrospinal fluid and plasma.The journal of headache and pain · 2025Article
- Migraine in men.The journal of headache and pain · 2025Review
- Understanding Headaches Attributed to Cranial and/or Cervical Vascular Disorders: Insights and Challenges for Neurologists.Pain and therapy · 2024Review
- Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1Acta neuropathologica communications · 2024Article
- Meningeal brain borders and migraine headache genesis.Trends in neurosciences · 2024Review
- Molecular nociceptive mechanisms in migraine: The migraine cascade.European journal of neurology · 2024Review
- Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2Molecular medicine reports · 2024Article
- Atogepant: Mechanism of action, clinical and translational science.Clinical and translational science · 2024Review
- Migraine: Advances in the Pathogenesis and Treatment.Neurology international · 2023Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains unclear whether intracellular cAMP signalling requires CGRP receptor activation during a migraine attack in humans. To address this question, we conducted a randomized, double-blind, placebo-controlled, parallel trial using a human provocation model involving the administration of CGRP and cilostazol in individuals with migraine pretreated with erenumab or placebo. Our study revealed that migraine attacks can be provoked in patients by cAMP-mediated mechanisms using cilostazol, even when the CGRP receptor is blocked by erenumab. Furthermore, the dilation of cranial arteries induced by cilostazol was not influenced by the CGRP receptor blockade. These findings provide clinical evidence that cAMP-evoked migraine attacks do not require CGRP receptor activation. This discovery opens up new possibilities for the development of mechanism-based drugs for the treatment of migraine.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.