Evidence map›Paper›PMID 28560313›Full record

ArticleeNeuro

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents.

Nicolas Montalbetti, Anna C Rued, Stefanie N Taiclet, Lori A Birder, F Aura Kullmann, Marcelo D Carattino

Open access · goldAbstract read
In one paragraph

Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.8field-weighted citation impact, top 4% 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.

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

28 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Real-Time Void Spot Assay.Journal of visualized experiments : JoVE · 2023
    Article
  11. Article
  12. Article
  13. Bladder infection with uropathogenicAmerican journal of physiology. Renal physiology · 2022
    Article
  14. Review
  15. Acid-sensing ion channels modulate bladder nociception.American journal of physiology. Renal physiology · 2021
    Article
  16. Article
  17. Article
  18. Review
  19. 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
  20. 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

6 authors at 1 institution in 1 country.

Nicolas MontalbettiRenal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.ORCID 0000-0003-2897-9540
Anna C RuedRenal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
Stefanie N TaicletRenal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
Lori A BirderRenal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
F Aura KullmannRenal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
Marcelo D CarattinoRenal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.ORCID 0000-0003-1901-1618
University of Pittsburgh · US

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Bladder Mucosal Dysfunction During AgingR01AG056944 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI APODACA, GERARD L, BIRDER, LORI A · 2018 to 2022
$3.2M
Biology and Function of the Bladder Umbrella Cell Paracellular BarrierR01DK099196 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI APODACA, GERARD L, CARATTINO, MARCELO DANIEL · 2013 to 2016
$1.7M
Conformational rearrangements underlying ASIC1a gatingR01DK084060 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CARATTINO, MARCELO DANIEL · 2010 to 2014
$1.6M
NIA NIH HHS R01 AG056944NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK084060NIDDK NIH HHS R01 DK099196
6 · The paper itself

Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain.

Indexed as

Action PotentialsAnimalsClaudinsCystitisDisease Models, AnimalFemaleHyperalgesiaMAP Kinase Signaling SystemNeural PathwaysNeurons, AfferentPatch-Clamp TechniquesPelvic PainPermeabilityRandom AllocationRats, Sprague-DawleySingle-Blind MethodClaudinsCldn2 protein, ratafferent innervationsDRG neuronsinterstitial cystitis/bladder pain syndromepaintetrodotoxinurinary bladder

Identifiers

PMID28560313
PMCPMC5442440
OpenAlexW2615390905

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.