Evidence map›Paper›PMID 42650796›Full record

ArticleBiomolecules2026

Pharmacological Modulation of the Kynurenine Pathway Using PF-04859989 Modulates PACAP Signaling in Migraine-Relevant Trigeminal Sensitization.

Evelin Vágvölgyi-Sümegi, Gábor Nagy-Grócz, Zsolt Galla, Edina Katalin Cseh, Zoltán István Tapody, Péter Monostori, János Tajti, Péter Klivényi, László Vécsei, Tamás Körtési

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In one paragraph

Article in Biomolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from 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.

2 · The registry

The trial behind it

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Evelin Vágvölgyi-SümegiDepartment of Theoretical Health Sciences and Health Management, Faculty of Health Sciences and Social Studies, University of Szeged, Temesvári krt. 31, H-6726 Szeged, Hungary.ORCID 0009-0006-5808-5600
Gábor Nagy-GróczDepartment of Theoretical Health Sciences and Health Management, Faculty of Health Sciences and Social Studies, University of Szeged, Temesvári krt. 31, H-6726 Szeged, Hungary.ORCID 0000-0003-2121-4625
Zsolt GallaMetabolic and Newborn Screening Laboratory, Department of Pediatrics, University of Szeged, Korányi Fasor 14-15, H-6720 Szeged, Hungary.
Edina Katalin CsehDepartment of Neurology, Albert Szent-Györgyi Faculty of Medicine and Clinical Center, University of Szeged, H-6725 Szeged, Hungary.
Zoltán István TapodyDepartment of Theoretical Health Sciences and Health Management, Faculty of Health Sciences and Social Studies, University of Szeged, Temesvári krt. 31, H-6726 Szeged, Hungary.ORCID 0009-0002-1239-0600
Péter MonostoriMetabolic and Newborn Screening Laboratory, Department of Pediatrics, University of Szeged, Korányi Fasor 14-15, H-6720 Szeged, Hungary.ORCID 0000-0003-3591-6054
János TajtiDepartment of Neurology, Albert Szent-Györgyi Faculty of Medicine and Clinical Center, University of Szeged, H-6725 Szeged, Hungary.
Péter KlivényiHUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, Danube Neuroscience Research Laboratory, University of Szeged, Tisza Lajos krt. 113, H-6725 Szeged, Hungary.ORCID 0000-0002-5389-3266
László VécseiHUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, Danube Neuroscience Research Laboratory, University of Szeged, Tisza Lajos krt. 113, H-6725 Szeged, Hungary.
Tamás KörtésiDepartment of Theoretical Health Sciences and Health Management, Faculty of Health Sciences and Social Studies, University of Szeged, Temesvári krt. 31, H-6726 Szeged, Hungary.

Funding

HUN-REN-SZTE Neuroscience Research Group 2000607University of Szeged 8811
6 · The paper itself

Abstract

backgroundMigraine is a disabling neurological disorder in which neuropeptides, particularly pituitary adenylate cyclase-activating polypeptide (PACAP), play pathogenic roles. The kynurenine pathway (KP) is increasingly implicated in migraine-related glutamatergic and neuroinflammatory mechanisms. Previously, we showed that the neuroprotective metabolite kynurenic acid attenuates PACAP overexpression following trigeminovascular activation. This study investigated the effects of kynurenine aminotransferase II (KAT-II) inhibition on PACAP expression and KP metabolites during trigeminal sensitization.

methodsRats received Complete Freund's Adjuvant (CFA) or saline injection into the right whisker pad. KAT-II inhibitor PF-04859989 (16 and 32 mg/kg) or saline was administered intraperitoneally 72 h later. Blood samples and nucleus trigeminus caudalis (TNC) were collected for PACAP and KP quantification.

resultsCFA treatment induced significant PACAP overexpression in the TNC and altered peripheral KP metabolite levels. PF-04859989 further increased PACAP expression, reaching significance at the 16 mg/kg dose, whereas no significant additional effect was observed at 32 mg/kg. In parallel, treatment with PF-04859989 altered peripheral KP metabolite concentrations in the peripheral inflammatory model, predominantly at the lower dose.

conclusionsThis study demonstrates that KAT-II inhibition by PF-04859989 modulates PACAP signaling and KP metabolism under trigeminal inflammatory conditions. These findings support KP-PACAP interactions and may identify novel migraine-related therapeutic targets.

Indexed as

KynurenineMigraine DisordersPituitary Adenylate Cyclase-Activating PolypeptideAnimalsFreund's AdjuvantMaleRatsRats, Sprague-DawleySignal TransductionTransaminasesFreund's AdjuvantKynureninekynurenine-oxoglutarate transaminasePituitary Adenylate Cyclase-Activating PolypeptideTransaminaseskynurenic acidkynurenine aminotransferase IIkynurenine pathwaymigraineneuropeptidesPACAP

Identifiers

PMID42650796
PMCPMC13511012

What Socratic holds

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Registered trials

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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 Socratic graph.