Evidence map›Paper›PMID 40813451›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2025

Ro 64-6198, a selective NOP receptor agonist attenuates social impairments associated with NTG-induced migraine pain.

Akanksha Mudgal, Olga Wronikowska-Denysiuk, Madeline Martinez, Darian Peters, Maciej Maj, Isabel Snow, Diana Pietrzak-Mitura, Lawrence Toll, Akihiko Ozawa, Katarzyna M Targowska-Duda

Abstract read
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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.

Akanksha MudgalDepartment of Biopharmacy, Medical University of Lublin, Lublin, Poland.
Olga Wronikowska-DenysiukIndependent Laboratory of Behavioral Studies, Medical University of Lublin, Lublin, Poland.
Madeline MartinezDepartment of Biomedical Science, Florida Atlantic University, Boca Raton, FL, USA.
Darian PetersDepartment of Biomedical Science, Florida Atlantic University, Boca Raton, FL, USA.
Maciej MajDepartment of Biopharmacy, Medical University of Lublin, Lublin, Poland.
Isabel SnowDepartment of Biomedical Science, Florida Atlantic University, Boca Raton, FL, USA.
Diana Pietrzak-MituraDepartment of Biopharmacy, Medical University of Lublin, Lublin, Poland.
Lawrence TollDepartment of Biomedical Science, Florida Atlantic University, Boca Raton, FL, USA.
Akihiko OzawaDepartment of Biomedical Science, Florida Atlantic University, Boca Raton, FL, USA. aozawa@health.fau.edu.
Katarzyna M Targowska-DudaDepartment of Biopharmacy, Medical University of Lublin, Lublin, Poland. katarzyna.targowska-duda@umlub.pl.

Funding

Dissecting active neural circuits regulating sensory and affective painR34NS121875 · NINDS · FLORIDA ATLANTIC UNIVERSITY · PI OZAWA, AKIHIKO · 2021 to 2021
$673k
Narodowe Centrum Nauki (National Science Centre) 2021/42/E/NZ7/00191NINDS NIH HHS R34 NS121875U.S. Department of Defense (United States Department of Defense) W81XWH2110410U.S. Department of Health & Human Services | National Institutes of Health (NIH) R34NS121875
6 · The paper itself

Abstract

Migraine is a debilitating neurological disorder with significant impact on quality of life, including social functioning. This study investigated the effects of nitroglycerin (NTG)-induced migraine in male and female mice on social behavior and neuronal activation and explored the therapeutic potential of nociceptin opioid peptide (NOP) receptor agonism. We found that acute NTG administration induced mechanical allodynia in periorbital region and paw as well as impaired social behavior in both sexes, albeit with sex-specific patterns. The NOP receptor agonist, Ro 64-6198, reversed both the allodynia and social deficits induced by NTG. The reversal of social impairment elicited by Ro 64-6198 was partially blocked by the NOP receptor antagonist, SB-612111, confirming NOP receptor-mediated action. Using TRAP2/Ai9 transgenic mice, we demonstrated that NTG induced significant neuronal activation in brain regions associated with pain and social behavior, including the anterior cingulate cortex, amygdala, hippocampus, hypothalamus, and periaqueductal gray (in female mice) as well as trigeminal nucleus caudalis (TNC) in male and female mice. Consistent with the behavioral results, NTG-induced neuronal activation in these brain regions was significantly reduced in the presence of Ro 64-6198. Our findings provide further evidence for the involvement of the NOP system in migraine pathophysiology, particularly social aspects that are indirectly pain-related symptoms, and provide a direct correlation with neuronal activation in several brain regions.

Indexed as

Migraine DisordersReceptors, OpioidSocial BehaviorSpiro CompoundsAnimalsBrainDisease Models, AnimalFemaleHyperalgesiaImidazolesMaleMiceMice, Inbred C57BLMice, TransgenicNitroglycerinNociceptin ReceptorImidazolesNitroglycerinNociceptin ReceptorOprl1 protein, mouseReceptors, OpioidRo 64-6198Spiro Compounds

Identifiers

PMID40813451
PMCPMC12603126

What OpenQuestion 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 OpenQuestion graph.