ArticleJCI insight2018
Chronic linaclotide treatment reduces colitis-induced neuroplasticity and reverses persistent bladder dysfunction.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Efficacy and safety of Guanylyl cyclase C agonists (linaclotide and plecanatide) in patients with irritable bowel syndrome with constipation: a systematic review and meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2026Pooled it
- Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation.The American journal of gastroenterology · 2021Trial
- Randomised clinical trial: linaclotide vs placebo-a study of bi-directional gut and brain axis.Alimentary pharmacology & therapeutics · 2020Trial
- Irritable bowel syndrome subtype predicts treatment response and defines distinct mechanistic phenotypes in OAB-IBS comorbidity: a prospective observational study.World journal of urology · 2026Observational
- Evaluation of corneal morphology, pupillometry, and ocular surface parameters in Fabry disease patients: correlation with plasma Lyso-Gb3 levels.International ophthalmology · 2026Article
- From Epithelial Sensing to Visceral Pain: Neuropod and Enterochromaffin Cells in Gut Neuroepithelial Circuits.International journal of molecular sciences · 2026Review
- Akkermansia muciniphila drives viscero-visceral crosstalk via 5-HTExperimental & molecular medicine · 2026Article
- GABAExperimental physiology · 2026Article
- Influence of Sacral and Thoracolumbar Spinal Nerve Electrical Stimulation on Colonic Motility in Anesthetized Yucatan Male Pigs.Neurogastroenterology and motility · 2026Article
- Splanchnic and Pelvic Spinal Afferent Pathways Relay Sensory Information From the Mouse Colorectum Into Distinct Brainstem Circuits.Journal of neurochemistry · 2025Article
- Article
- Acute urinary tract infection elicits bladder afferent hypersensitivity.Brain, behavior, & immunity - health · 2025Article
- Review
- Discovery of a Small Molecule Activator of Slack (Kcnt1) Potassium Channels That Significantly Reduces Scratching in Mouse Models of Histamine-Independent and Chronic Itch.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Fundamental Neurochemistry Review: The role of enteroendocrine cells in visceral pain.Journal of neurochemistry · 2023Review
- Endometriosis-Related Chronic Pelvic Pain.Biomedicines · 2023Review
- Article
- Review
- Intestinal neuropod cell GUCY2C regulates visceral pain.The Journal of clinical investigation · 2023Article
- Animal models of interstitial cystitis/bladder pain syndrome.Frontiers in physiology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Irritable bowel syndrome (IBS) patients suffer from chronic abdominal pain and extraintestinal comorbidities, including overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC-PBS). Mechanistic understanding of the cause and time course of these comorbid symptoms is lacking, as are clinical treatments. Here, we report that colitis triggers hypersensitivity of colonic afferents, neuroplasticity of spinal cord circuits, and chronic abdominal pain, which persists after inflammation. Subsequently, and in the absence of bladder pathology, colonic hypersensitivity induces persistent hypersensitivity of bladder afferent pathways, resulting in bladder-voiding dysfunction, indicative of OAB/IC-PBS. Daily administration of linaclotide, a guanylate cyclase-C (GC-C) agonist that is restricted to and acts within the gastrointestinal tract, reverses colonic afferent hypersensitivity, reverses neuroplasticity-induced alterations in spinal circuitry, and alleviates chronic abdominal pain in mice. Intriguingly, daily linaclotide administration also reverses persistent bladder afferent hypersensitivity to mechanical and chemical stimuli and restores normal bladder voiding. Linaclotide itself does not inhibit bladder afferents, rather normalization of bladder function by daily linaclotide treatment occurs via indirect inhibition of bladder afferents via reduced nociceptive signaling from the colon. These data support the concepts that cross-organ sensitization underlies the development and maintenance of visceral comorbidities, while pharmaceutical treatments that inhibit colonic afferents may also improve urological symptoms through common sensory pathways.
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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.