Evidence map›Paper›PMID 40016124›Full record

ArticleJournal of neuroendocrinology2025

Estrogens produced within the central amygdala inhibit varicella zoster-induced orofacial pain.

Phillip Kramer, Lauren Nguyen, Paul R Kinchington

Abstract read
In one paragraph

Article in Journal of neuroendocrinology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

3 authors.

Phillip KramerDepartment of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, Texas, USA.ORCID 0000-0003-0117-542X
Lauren NguyenDepartment of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, Texas, USA.
Paul R KinchingtonDepartments of Ophthalmology and of Molecular Microbiology and Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
Varicella zoster virus-Induced Pain in a Rat Model of Post-Herpetic NeuralgiaR01NS064022 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KINCHINGTON, PAUL R. · 2009 to 2019
$3.6M
Estradiol and Zoster Associated Orofacial PainR01DE026749 · NIDCR · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI KRAMER, PHILLIP R · 2018 to 2022
$2.0M
Estrogen and TMJ PainR01DE022129 · NIDCR · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI KRAMER, PHILLIP R · 2012 to 2015
$1.6M
Varicella zoster virus-Induced Pain in a Rat Model of Post-Herpetic NeuralgiaR56NS064022 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KINCHINGTON, PAUL R. · 2015 to 2015
$532k
NEI NIH HHS P30 EY008098NIDCR NIH HHS R01 DE022129NIDCR NIH HHS R01 DE026749NIH HHS DE022129NIH HHS EY08098NIH HHS NS064022NINDS NIH HHS R01 NS064022NINDS NIH HHS R56 NS064022
6 · The paper itself

Abstract

Varicella zoster virus (VZV) causes chicken pox, and reactivation of this virus later in life causes shingles. Previous work demonstrated that estrogens could reduce VZV-induced orofacial pain and affect gene expression in the central amygdala. It is known that the central amygdala processes pain signals from the orofacial region and that estrogens produced by the enzyme aromatase within the central amygdala regulate neuronal function. Based on the previous studies, it was hypothesized estrogens produced within the central amygdala attenuate VZV-induced orofacial pain. To address this hypothesis, male Long-Evans rats were implanted with cannulas terminating in the central amygdala. Through these cannulas, the aromatase inhibitor letrozole or estrogen receptor alpha (ERα) agonist, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), was infused in the central amygdala. The whisker pad of each rat was injected with either MeWo cells or MeWo cells containing VZV. One week after VZV injection, letrozole or PPT was infused into the central amygdala, followed by measuring pain behavior, GABA release, and estradiol concentrations. Tissues in the orofacial pain pathway were isolated, and neuronal activity was quantitated by counting c-Fos-positive neurons. Letrozole significantly increased the pain response and decreased GABA release. Letrozole also decreased estradiol within the central amygdala. Infusion of PPT reduced pain and increased GABA release. Moreover, letrozole increased the number of active neurons in the lateral parabrachial nucleus and spinal trigeminal nucleus, while PPT reduced the number of active neurons in the trigeminal ganglia, lateral parabrachial nucleus, and spinal trigeminal nucleus. The results suggest aromatase-derived estradiol interacts with ERα within the central amygdala to attenuate VZV-induced pain by increasing GABA release and reducing neuronal activity in the pain pathway.

Indexed as

Central Amygdaloid NucleusEstrogensFacial PainAnimalsAromatase InhibitorsEstrogen Receptor alphaHerpesvirus 3, HumanLetrozoleMaleNitrilesPhenolsPyrazolesRatsRats, Long-EvansTriazoles4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenolAromatase InhibitorsEstrogen Receptor alphaEstrogensLetrozoleNitrilesPhenolsPyrazolesTriazolesamygdalaaromataseestrogenorofacialpain

Identifiers

PMID40016124
PMCPMC12045675

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.