ArticleCephalalgia : an international journal of headache2020
Fluorescently-labeled fremanezumab is distributed to sensory and autonomic ganglia and the dura but not to the brain of rats with uncompromised blood brain barrier.
Article in Cephalalgia : an international journal of headache, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- Effectiveness and safety of anti-CGRP monoclonal antibodies in hemiplegic migraine: an individual patient quantitative analysis.The journal of headache and pain · 2026Pooled it
- Safety and Efficacy of Fremanezumab for the Prevention of Migraine: A Meta-Analysis From Randomized Controlled Trials.Frontiers in neurology · 2020Pooled it
- Calcitonin gene-related peptide induces headache attacks in people with idiopathic intracranial hypertension.Brain : a journal of neurology · 2026Trial
- Effects of erenumab on migraine aura frequency: a REFORM study.The journal of headache and pain · 2026Trial
- Double-blind, randomized, placebo-controlled study to evaluate erenumab-specific central effects: an fMRI study.The journal of headache and pain · 2024Trial
- Longitudinal changes in functional connectivity and pain-induced brain activations in patients with migraine: a functional MRI study pre- and post- treatment with Erenumab.The journal of headache and pain · 2022Trial
- CGRP-induced migraine-like headache in persistent post-traumatic headache attributed to mild traumatic brain injury.The journal of headache and pain · 2022Trial
- Trial
- Ultrasound assessment of cerebrovascular risk via breath-holding index in migraine patients treated with anti-CGRP monoclonal antibodies: a pilot study.Journal of ultrasonography · 2026Article
- Neurologic Symptoms and Cerebrovascular Events During Atogepant Therapy: A Case Series with Contextual Comparison with a Non-Gepant-Treated Migraine Cohort.Journal of clinical medicine · 2026Article
- Hypothalamic and sex-related hormones in migraine.The journal of headache and pain · 2026Review
- Targeting glial-orchestrated neuroinflammation in migraine pathophysiology.The journal of headache and pain · 2026Review
- Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization.Frontiers in immunology · 2026Review
- The vessel-to-neuron trigeminovascular hypothesis of migraine pathogenesis - the 'pro' argument.The journal of headache and pain · 2025Review
- Review
- Calcitonin Gene-Related Peptide (CGRP)-Expressing Neurons in the External Lateral Parabrachial Area Regulate Pain-Induced Sleep Disturbances.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CGRP-Targeted Migraine Therapies in Patients With Vascular Risk Factors or Stroke: A Review.Neurology · 2025Review
- Unmasking the relationship between CGRP and glutamate: from peripheral excitation to central sensitization in migraine.The journal of headache and pain · 2025Review
- Is there a role of calcitonin gene-related peptide in cortical spreading depression mechanisms?- argument con.The journal of headache and pain · 2025Article
- Is there a role of calcitonin gene-related peptide in cortical spreading depression mechanisms?- Argument pro.The journal of headache and pain · 2025Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe presence of calcitonin gene-related peptide and its receptors in multiple brain areas and peripheral tissues previously implicated in migraine initiation and its many associated symptoms raises the possibility that humanized monoclonal anti-calcitonin gene-related peptide antibodies (CGRP-mAbs) can prevent migraine by modulating neuronal behavior inside and outside the brain. Critical to our ability to conduct a fair discussion over the mechanisms of action of CGRP-mAbs in migraine prevention is data generation that determines which of the many possible peripheral and central sites are accessible to these antibodies - a question raised frequently due to their large size. MATERIAL AND
methodsRats with uncompromised and compromised blood-brain barrier (BBB) were injected with Alexa Fluor 594-conjugated fremanezumab (Frema594), sacrificed 4 h or 7 d later, and relevant tissues were examined for the presence of Frema594.
resultsIn rats with uncompromised BBB, Frema594 was similarly observed at 4 h and 7 d in the dura, dural blood vessels, trigeminal ganglion, C2 dorsal root ganglion, the parasympathetic sphenopalatine ganglion and the sympathetic superior cervical ganglion but not in the spinal trigeminal nucleus, thalamus, hypothalamus or cortex. In rats with compromised BBB, Frema594 was detected in the cortex (100 µm surrounding the compromised BBB site) 4 h but not 7 d after injections. DISCUSSION: Our inability to detect fluorescent (CGRP-mAbs) in the brain supports the conclusion that CGRP-mAbs prevent the headache phase of migraine by acting mostly, if not exclusively, outside the brain as the amount of CGRP-mAbs that enters the brain (if any) is too small to be physiologically meaningful.
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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.