ArticlePain2020
Fremanezumab and its isotype slow propagation rate and shorten cortical recovery period but do not prevent occurrence of cortical spreading depression in rats with compromised blood-brain barrier.
Article in Pain, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Effects of erenumab on migraine aura frequency: a REFORM study.The journal of headache and pain · 2026Trial
- CGRP-targeted migraine treatment and early pathophysiology in experimental subarachnoid hemorrhage.The journal of headache and pain · 2026Article
- Is canonical SD a clinically relevant model of migraine? Argument con.The journal of headache and pain · 2025Review
- Is canonical SD a clinically relevant model of migraine? Argument pro.The journal of headache and pain · 2025Review
- Spreading depolarization as a therapeutic target in migraine.Nature reviews. Neurology · 2025Review
- The mysterious link between migraine aura and migraine headache.PLoS biology · 2025Article
- Is there a role of calcitonin gene-related peptide in cortical spreading depression mechanisms?- argument con.The journal of headache and pain · 2025Article
- Efficacy of anti-calcitonin gene-related peptide monoclonal antibodies in hemiplegic migraine: a case report and review of literature.Frontiers in neurology · 2025Article
- Molecular and Cellular Neurobiology of Spreading Depolarization/Depression and Migraine: A Narrative Review.International journal of molecular sciences · 2024Review
- Are anti-calcitonin gene-related peptide monoclonal antibodies effective in treating migraine aura? A pilot prospective observational cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Observational
- Calcitonin gene-related peptide causes migraine aura.The journal of headache and pain · 2023Article
- Ten open questions in migraine prophylaxis with monoclonal antibodies blocking the calcitonin-gene related peptide pathway: a narrative review.The journal of headache and pain · 2023Review
- Rodent behavior following a dural inflammation model with anti-CGRP migraine medication treatment.Frontiers in neurology · 2023Article
- Antiseizure Medications for the Prophylaxis of Migraine during the Anti- CGRP Drugs Era.Current neuropharmacology · 2023Review
- Calcitonin gene-related peptide (CGRP) is a key molecule released in acute migraine attacks-Successful translation of basic science to clinical practice.Journal of internal medicine · 2022Review
- Exploring the neurobiology of the premonitory phase of migraine preclinically - a role for hypothalamic kappa opioid receptors?The journal of headache and pain · 2022Article
- Gepants - a long way to cure: a narrative review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Review
- Dysregulation of serum prolactin links the hypothalamus with female nociceptors to promote migraine.Brain : a journal of neurology · 2022Article
- Could the New Anti-CGRP Monoclonal Antibodies Be Effective in Migraine Aura? Case Reports and Literature Review.Journal of clinical medicine · 2022Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Most centrally acting migraine preventive drugs suppress frequency and velocity of cortical spreading depression (CSD). The purpose of the current study was to determine how the new class of peripherally acting migraine preventive drug (ie, the anti-CGRP-mAbs) affect CSD-an established animal model of migraine aura, which affects about 1/3 of people with migraine-when allowed to cross the blood-brain barrier (BBB). Using standard electrocorticogram recording techniques and rats in which the BBB was intentionally compromised, we found that when the BBB was opened, the anti-CGRP-mAb fremanezumab did not prevent the induction, occurrence, or propagation of a single wave of CSD induced by a pinprick, but that both fremanezumab and its isotype were capable of slowing down the propagation velocity of CSD and shortening the period of profound depression of spontaneous cortical activity that followed the spreading depolarization. Fremanezumab's inability to completely block the occurrence of CSD in animals in which the BBB was compromised suggests that calcitonin gene-related peptide (CGRP) may not be involved in the initiation of CSD, at least not to the extent that it can prevent its occurrence. Similarly, we cannot conclude that CGRP is involved in the propagation velocity or the neuronal silencing period (also called cortical recovery period) that follows the CSD because similar effects were observed when the isotype was used. These finding call for caution with interpretations of studies that claim to show direct central nervous system effects of CGRP-mAbs.
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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.