ReviewThe journal of headache and pain2023
Shared and independent roles of CGRP and PACAP in migraine pathophysiology.
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 48 papers, 5 of them syntheses that pooled 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.
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
48 citing papers in PubMed, 5 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Repurposed versus disease-specific medicinals for the prophylaxis of migraine: an updated systematic review.Pain management · 2025Pooled it
- Pooled it
- Lack of association between TRPV1 gene polymorphisms and risk of migraine chronification: a case-control study and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Pooled it
- The 200 most influential publications in migraine research: a bibliometric mapping of the intellectual landscape.Frontiers in neurology · 2025Pooled it
- Systematic review and meta-analysis on the efficacy and safety of rimegepant for migraine.Frontiers in neurologyPooled it
- PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial.The journal of headache and pain · 2025Trial
- Effects of PDE-3 inhibition in persistent post-traumatic headache: evidence of cAMP-dependent signaling.The journal of headache and pain · 2024Trial
- Hypersensitivity to PACAP-38 in post-traumatic headache: a randomized clinical trial.Brain : a journal of neurology · 2024Trial
- Pharmacological Modulation of the Kynurenine Pathway Using PF-04859989 Modulates PACAP Signaling in Migraine-Relevant Trigeminal Sensitization.Biomolecules · 2026Article
- A delayed endothelial-glial mechanism for CGRP-induced migraine.The journal of headache and pain · 2026Review
- Article
- New Directions in Migraine Pathophysiology: The Glymphatic System and PACAP.Life (Basel, Switzerland) · 2026Review
- Overlapping pathways of migraine and the endocannabinoid system: Potential therapeutic targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Calcitonin gene-related peptide as a neuroimmune amplifier in allergic rhinitis: from disease worsening to targeted drug intervention.Frontiers in immunology · 2026Review
- Biofluid-based predictors of post-concussion symptoms: a narrative review of mild traumatic brain injury biomarkers.Brain communications · 2026Review
- CGRP and Migraine: Real-World Insights and Future Therapeutic Directions.Annual review of medicine · 2026Review
- Impaired meningeal lymphatic drainage correlates with headache intensity in episodic migraine.The journal of headache and pain · 2025Article
- Cerebrospinal fluid draining lymphatics in health and disease: advances and controversies.Nature cardiovascular research · 2025Review
- PACAP versus CGRP in migraine: From mouse models to clinical translation.Cephalalgia : an international journal of headache · 2025Review
- Mechanistic intersections between migraine and major depressive disorder.The journal of headache and pain · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The neuropeptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have emerged as mediators of migraine pathogenesis. Both are vasodilatory peptides that can cause migraine-like attacks when infused into people and migraine-like symptoms when injected into rodents. In this narrative review, we compare the similarities and differences between the peptides in both their clinical and preclinical migraine actions. A notable clinical difference is that PACAP, but not CGRP, causes premonitory-like symptoms in patients. Both peptides are found in distinct, but overlapping areas relevant to migraine, most notably with the prevalence of CGRP in trigeminal ganglia and PACAP in sphenopalatine ganglia. In rodents, the two peptides share activities, including vasodilation, neurogenic inflammation, and nociception. Most strikingly, CGRP and PACAP cause similar migraine-like symptoms in rodents that are manifested as light aversion and tactile allodynia. Yet, the peptides appear to act by independent mechanisms possibly by distinct intracellular signaling pathways. The complexity of these signaling pathways is magnified by the existence of multiple CGRP and PACAP receptors that may contribute to migraine pathogenesis. Based on these differences, we suggest PACAP and its receptors provide a rich set of targets to complement and augment the current CGRP-based migraine therapeutics.
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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.