Evidence map›Paper›PMID 37370051›Full record

ReviewThe journal of headache and pain2023

Future targets for migraine treatment beyond CGRP.

Linda Al-Hassany, Deirdre M Boucherie, Hannah Creeney, Ruben W A van Drie, Fatemeh Farham, Silvia Favaretto, Cédric Gollion, Lou Grangeon, Hannah Lyons, Karol Marschollek and 8 more

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The journal of headache and pain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
10.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

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  5. The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 12 institutions in 9 countries.

Linda Al-HassanyDepartment of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Deirdre M BoucherieDepartment of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Hannah CreeneyWolfson Centre for Age-Related Diseases, King's College London, London, UK.
Ruben W A van DrieDepartment of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Fatemeh FarhamDepartment of Headache, Iranian Centre of Neurological Researchers, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Silvia FavarettoHeadache Center, Neurology Clinic, University Hospital of Padua, Padua, Italy.
Cédric GollionDepartment of Neurology, University Hospital of Toulouse, Toulouse, France.
Lou GrangeonNeurology Department, Rouen University Hospital, Rouen, France.
Hannah LyonsInstitute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Karol MarschollekDepartment of Neurology, Wroclaw Medical University, Wrocław, Poland.
Dilara OnanSpine Health Unit, Faculty of Physical Therapy and Rehabilitation, Hacettepe University, Ankara, Turkey.
Umberto PensatoNeurology and Stroke Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
Emily StanyerWolfson Centre for Age-Related Diseases, King's College London, London, UK.
Marta Waliszewska-ProsółDepartment of Neurology, Wroclaw Medical University, Wrocław, Poland.
Wietse WielsFaculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Hui Zhou ChenWolfson Centre for Age-Related Diseases, King's College London, London, UK.
Faisal Mohammad AminDanish Headache Center, Department of Neurology, Faculty of Health and Medical Sciences, Rigshospitalet Glostrup, University of Copenhagen, Copenhagen, Denmark. faisal@dadlnet.dk.
European Headache Federation School of Advanced Studies (EHF-SAS)
Erasmus MC · NLKing's College London · GBWroclaw Medical University · PLHacettepe University · TRHumanitas University · ITRigshospitalet · DKTehran University of Medical Sciences · IRUniversité de Rouen Normandie · FRUniversité Fédérale de Toulouse Midi-Pyrénées · FRUniversity of Birmingham · GBUniversity of Padua · ITVrije Universiteit Brussel · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMigraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine.

findingsWe covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a PAC

conclusionWhile current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients.

Indexed as

Headache DisordersMigraine DisordersAdrenomedullinCalcitonin Gene-Related PeptideHumansIslet Amyloid PolypeptidePituitary Adenylate Cyclase-Activating PolypeptideReceptors, Calcitonin Gene-Related PeptideAdrenomedullinCalcitonin Gene-Related PeptideIslet Amyloid PolypeptidePituitary Adenylate Cyclase-Activating PolypeptideReceptors, Calcitonin Gene-Related PeptideAdrenomedullinAmylinIon channelsMigraineNitric oxideNon-CGRP targetsPhosphodiesterasesPituitary adenylate cyclase-activating polypeptideVasoactive intestinal polypeptide

Identifiers

PMID37370051
PMCPMC10304392
OpenAlexW4382196834

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.