Evidence map›Paper›PMID 31091120›Full record

ArticleAmerican journal of physiology. Renal physiology2019

Cystitis-induced bladder pain is Toll-like receptor 4 dependent in a transgenic autoimmune cystitis murine model: a MAPP Research Network animal study.

Xiangrong Cui, Xuan Jing, Susan K Lutgendorf, Catherine S Bradley, Andrew Schrepf, Bradley A Erickson, Vincent A Magnotta, Timothy J Ness, Karl J Kreder, Michael A O'Donnell and 1 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04313972 (IC PaIN Trial), which is not on this map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.7field-weighted citation impact, top 11% 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.

NCT04313972 phase4terminatednot on this mapstarted 2021, after this paper: background citation

IC PaIN Trial: Interstitial Cystitis Pain Improvement With Naltrexone, the Effect of Low Dose Naltrexone on Symptoms and Pain of Patients With Interstitial Cystitis/Painful Bladder Syndrome a Randomized Placebo-controlled Prospective Trial

TypeinterventionalSponsorEndeavor HealthRan2021 to 2023Enrolled3ConditionsInterstitial Cystitis, Painful Bladder Syndrome, Bladder Pain Syndrome, Low Dose NaltrexoneArmslow-dose naltrexone, Placebo oral tablet
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 26 citations in OpenAlex.

  1. Animal Models of Hunner-Type Interstitial Cystitis.International journal of urology : official journal of the Japanese Urological Association · 2026
    Review
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  5. Role of local angiotensin II signaling in bladder function.American journal of physiology. Renal physiology · 2024
    Review
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  7. Article
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  18. Interstitial cystitis/bladder pain syndrome: The evolving landscape, animal models and future perspectives.International journal of urology : official journal of the Japanese Urological Association · 2020
    Review
  19. Review
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

11 authors at 2 institutions in 1 country.

Xiangrong CuiDepartment of Urology, University of Iowa , Iowa City, Iowa.
Xuan JingDepartment of Urology, University of Iowa , Iowa City, Iowa.
Susan K LutgendorfDepartment of Urology, University of Iowa , Iowa City, Iowa.
Catherine S BradleyDepartment of Urology, University of Iowa , Iowa City, Iowa.
Andrew SchrepfDepartment of Psychological and Brain Sciences, University of Iowa , Iowa City, Iowa.
Bradley A EricksonDepartment of Urology, University of Iowa , Iowa City, Iowa.
Vincent A MagnottaDepartment of Radiology, University of Iowa , Iowa City, Iowa.
Timothy J NessDepartment of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham , Birmingham, Alabama.
Karl J KrederDepartment of Urology, University of Iowa , Iowa City, Iowa.
Michael A O'DonnellDepartment of Urology, University of Iowa , Iowa City, Iowa.
Yi LuoDepartment of Urology, University of Iowa , Iowa City, Iowa.ORCID 0000-0002-4013-6805
University of Iowa · USUniversity of Alabama at Birmingham · US

Funding

Urology Chronic Pelvic Pain Longitudinal Symptom Patterns StudyU01DK082344 · NIDDK · UNIVERSITY OF IOWA · PI KREDER, KARL J · 2008 to 2021
$9.8M
WSU Urologic Chronic Pelvic Pain Syndromes Discovery CenterU01DK082325 · NIDDK · WASHINGTON STATE UNIVERSITY · PI BOGIC, MARIJA · 2008 to 2021
$9.0M
Inhibition of TLR4 for Treatment of Cystitis PainR01DK111396 · NIDDK · UNIVERSITY OF IOWA · PI LUO, YI · 2017 to 2020
$1.4M
NIDDK NIH HHS R01 DK111396NIDDK NIH HHS U01 DK082325NIDDK NIH HHS U01 DK082344
6 · The paper itself

Abstract

Altered Toll-like receptor (TLR)4 activation has been identified in several chronic pain conditions but has not been well studied in interstitial cystitis/bladder pain syndrome (IC/BPS). Our previously published human studies indicated that patients with IC/BPS present altered systemic TLR4-mediated inflammatory responses, which were significantly correlated with reported pain severity. In the present study, we sought to determine whether altered TLR4 activation plays a role in pelvic/bladder pain seen in patients with IC/BPS using our validated IC/BPS-like transgenic autoimmune cystitis model (URO-OVA). URO-OVA mice developed responses consistent with pelvic and bladder pain after cystitis induction, which was associated with increased splenocyte production of TLR4-mediated proinflammatory cytokines IL-1β, IL-6, and TNF-α. Increased spinal expression of mRNAs for proinflammatory cytokines IL-6 and TNF-α, glial activation markers CD11b and glial fibrillary acidic protein, and endogenous TLR4 ligand high mobility group box 1 was also observed after cystitis induction. Compared with URO-OVA mice, TLR4-deficient URO-OVA mice developed significantly reduced nociceptive responses, although similar bladder inflammation and voiding dysfunction, after cystitis induction. Intravenous administration of TAK-242 (a TLR4-selective antagonist) significantly attenuated nociceptive responses in cystitis-induced URO-OVA mice, which was associated with reduced splenocyte production of TLR4-mediated IL-1β, IL-6, and TNF-α as well as reduced spinal expression of mRNAs for IL-6, TNF-α, CD11b, glial fibrillary acidic protein, and high mobility group box 1. Our results indicate that altered TLR4 activation plays a critical role in bladder nociception independent of inflammation and voiding dysfunction in the URO-OVA model, providing a potential mechanistic insight and therapeutic target for IC/BPS pain.

Indexed as

Pain ThresholdAnalgesicsAnimalsAutoimmune DiseasesCells, CulturedCystitis, InterstitialCytokinesDisease Models, AnimalInflammation MediatorsMice, Inbred C57BLMice, KnockoutNociceptive PainOvalbuminSignal TransductionSpineSpleenAnalgesicsCytokinesethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylateInflammation MediatorsOvalbuminSulfonamidesTlr4 protein, mouseToll-Like Receptor 4cystitismodelMultidisciplinary Approach to the Study of Chronic Pelvic PainpainToll-like receptor 4

Identifiers

PMID31091120
PMCPMC6692719
OpenAlexW2945129973

What OpenQuestion holds

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Read underepoch 390

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.