ReviewNeurogastroenterology and motility2014
Site and mechanism of morphine tolerance in the gastrointestinal tract.
Review in Neurogastroenterology and motility, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled 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.
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
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- Effect of perioperative dexmedetomidine on recovery of postoperative gastrointestinal function in patients with general anesthesia: a systematic review and meta-analysis.BMC anesthesiology · 2024Pooled it
- Acupuncture for postoperative gastrointestinal dysfunction in cancer: a systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Opioid-Induced Constipation: Mechanistic Insights, Experimental Models, and Future Perspectives.Biomedicines · 2026Review
- Article
- Impact of antibiotic-induced gut microbiota modulation on morphine analgesia, tolerance, withdrawal, and neurophysiological changes in mice.Scientific reports · 2025Article
- Comprehensive Analysis of Strong Opioid Side Effects in Palliative Care Using the SIDER Database.Journal of clinical medicine · 2025Article
- Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.bioRxiv : the preprint server for biology · 2024Article
- Review
- Insights into the Current and Possible Future Use of Opioid Antagonists in Relation to Opioid-Induced Constipation and Dysbiosis.Molecules (Basel, Switzerland) · 2023Review
- Postoperative Opioid Use Is Associated with Increased Rates of Grade B/C Pancreatic Fistula After Distal Pancreatectomy.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2023Article
- Opioid Analgesia and Opioid-Induced Adverse Effects: A Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The Guts of the Opioid Crisis.Physiology (Bethesda, Md.) · 2021Article
- Management of Opioid-Induced Constipation and Bowel Dysfunction: Expert Opinion of an Italian Multidisciplinary Panel.Advances in therapy · 2021Review
- Evidence for Modulation of Substance Use Disorders by the Gut Microbiome: Hidden in Plain Sight.Pharmacological reviews · 2021Review
- Medications Development for Treatment of Opioid Use Disorder.Cold Spring Harbor perspectives in medicine · 2021Review
- Improved efficacy, tolerance, safety, and abuse liability profile of the combination of CR4056 and morphine over morphine alone in rodent models.British journal of pharmacology · 2020Article
- On the Role of Peripheral Sensory and Gut Mu Opioid Receptors: Peripheral Analgesia and Tolerance.Molecules (Basel, Switzerland) · 2020Review
- G-Protein-Coupled Receptors Are Dynamic Regulators of Digestion and Targets for Digestive Diseases.Gastroenterology · 2019Review
- Methylation Products of 6β- N-Heterocyclic Substituted Naltrexamine Derivatives as Potential Peripheral Opioid Receptor Modulators.ACS chemical neuroscience · 2018Article
- Loperamide cardiotoxicity: "A Brief Review".Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Opioid-induced constipation is a major clinical problem. The effects of morphine, and other narcotics, on the gastrointestinal tract persist over long-term use thus limiting the clinical benefit of these excellent pain relievers. The effects of opioids in the gut, including morphine, are largely mediated by the μ-opioid receptors at the soma and nerve terminals of enteric neurons. Recent studies demonstrate that regional differences exist in both acute and chronic morphine along the gastrointestinal tract. While tolerance develops to the analgesic effects and upper gastrointestinal motility upon repeated morphine administration, tolerance does not develop in the colon with chronic opioids resulting in persistent constipation. Here, we review the mechanisms by which tolerance develops in the small but not the large intestine. The regional differences lie in the signaling and regulation of the μ-opioid receptor in the various segments of the gastrointestinal tract. The differential role of β-arrestin2 in tolerance development between central and enteric neurons defines the potential for therapeutic approaches in developing ligands with analgesic properties and minimal constipating effects.
Indexed as
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What OpenQuestion holds
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.