ReviewThe journal of headache and pain2018
The big CGRP flood - sources, sinks and signalling sites in the trigeminovascular system.
Review in The journal of headache and pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 5 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
88 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Pooled it
- Efficacy and safety of calcitonin gene-related peptide antagonists in migraine treatment: A meta-analysis.Brain and behavior · 2022Pooled it
- Pooled it
- Global prevalence and pathogenesis of headache in COVID-19: A systematic review and meta-analysis.F1000Research · 2020Pooled it
- CGRP monoclonal antibody for preventive treatment of chronic migraine: An update of meta-analysis.Brain and behavior · 2019Pooled it
- Neurovascular-immune mediator dynamics in migraine: State-dependent effects of caffeine.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Trial
- Anti-CGRP receptor antibodies do not modulate trigeminal pain processing: indication for distinct mechanisms of CGRP pathway blockade.The journal of headache and pain · 2026Trial
- Trial
- Targeting the microbiome in pediatric migraine: gastrointestinal manifestations and the therapeutic role ofGut microbes · 2026Article
- Glymphatic-Hippocampal Axis Alterations Across the Migraine-Medication Exposure Continuum: A Multi-modal Neuroimaging Study.Pain and therapy · 2026Article
- Calcitonin gene-related peptide concentration in cerebrospinal fluid and serum in horses affected by trigeminal-mediated headshaking.Equine veterinary journal · 2026Article
- Cochlear Functional Changes and CGRP Modulation in a Chronic Nitroglycerin Migraine-Like Rat Model.The European journal of neuroscience · 2026Article
- New Directions in Migraine Pathophysiology: The Glymphatic System and PACAP.Life (Basel, Switzerland) · 2026Review
- Light-aversion and cephalic allodynia in an intravenous CGRP model of migraine-like behaviour in male and female rats.The journal of headache and pain · 2026Article
- Beyond AQP-4: convergent glymphatic-meningeal lymphatic dysfunction underlying multifactorial migraine pathogenesis.Frontiers in immunology · 2026Review
- Diffusion Tensor Imaging-Based Glymphatic Dysfunction Assessments in Migraine Syndromes: Mechanisms and Diagnostic Implications.Biomedicines · 2025Review
- Impaired meningeal lymphatic drainage correlates with headache intensity in episodic migraine.The journal of headache and pain · 2025Article
- Preanalytical stability of plasma calcitonin gene-related peptide: clinical and research implications.The journal of headache and pain · 2025Article
- Abnormal neurovascular coupling induces glymphatic dysfunction in a mouse model of familial hemiplegic migraine type 2.The journal of headache and pain · 2025Article
- The challenge of diagnosing intracranial pressure elevations as an otolaryngologist.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCalcitonin gene-related peptide (CGRP) has long been a focus of migraine research, since it turned out that inhibition of CGRP or CGRP receptors by antagonists or monoclonal IgG antibodies was therapeutic in frequent and chronic migraine. This contribution deals with the questions, from which sites CGRP is released, where it is drained and where it acts to cause its headache proliferating effects in the trigeminovascular system.
resultsThe available literature suggests that the bulk of CGRP is released from trigeminal afferents both in meningeal tissues and at the first synapse in the spinal trigeminal nucleus. CGRP may be drained off into three different compartments, the venous blood plasma, the cerebrospinal fluid and possibly the glymphatic system. CGRP receptors in peripheral tissues are located on arterial vessel walls, mononuclear immune cells and possibly Schwann cells; within the trigeminal ganglion they are located on neurons and glial cells; in the spinal trigeminal nucleus they can be found on central terminals of trigeminal afferents. All these structures are potential signalling sites for CGRP, where CGRP mediates arterial vasodilatation but not direct activation of trigeminal afferents. In the spinal trigeminal nucleus a facilitating effect on synaptic transmission seems likely. In the trigeminal ganglion CGRP is thought to initiate long-term changes including cross-signalling between neurons and glial cells based on gene expression. In this way, CGRP may upregulate the production of receptor proteins and pro-nociceptive molecules.
conclusionsCGRP and other big molecules cannot easily pass the blood-brain barrier. These molecules may act in the trigeminal ganglion to influence the production of pronociceptive substances and receptors, which are transported along the central terminals into the spinal trigeminal nucleus. In this way peripherally acting therapeutics can have a central antinociceptive effect.
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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.