ArticlePloS one2012
Morphine decreases enteric neuron excitability via inhibition of sodium channels.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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
35 citing papers in PubMed, 52 citations in OpenAlex.
- Opioid-Induced Constipation: Mechanistic Insights, Experimental Models, and Future Perspectives.Biomedicines · 2026Review
- Evaluation of AT121 versus morphine on cortical neurons electrophysiology and dopamine concentrations in hippocampal cells.PloS one · 2026Article
- Butyrate prevents chemotherapy-induced gastrointestinal toxicity and microbial dysbiosis.Scientific reports · 2025Article
- Butyrate Modulates Intestinal Microbiome and Epithelial Function to Attenuate Irinotecan-induced GI Toxicity.Research square · 2025Article
- Delayed Onset of Spinal Anesthesia in a Chronic Opioid User Undergoing Cesarean Section.Cureus · 2025Article
- The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Novel insights into mechanisms of inhibition of colonic motility by loperamide.Frontiers in neuroscience · 2024Article
- Chronic Morphine Induces IL-18 in Ileum Myenteric Plexus Neurons Through Mu-opioid Receptor Activation in Cholinergic and VIPergic Neurons.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
- Morphine-mediated release of astrocyte-derived extracellular vesicle miR-23a induces loss of pericyte coverage at the blood-brain barrier: Implications for neuroinflammation.Frontiers in cell and developmental biology · 2022Article
- The Cannabinoid Receptor Type 1 Positive Allosteric Modulator ZCZ011 Attenuates Naloxone-Precipitated Diarrhea and Weight Loss in Oxycodone-Dependent Mice.The Journal of pharmacology and experimental therapeutics · 2022Article
- Opioid Analgesia and Opioid-Induced Adverse Effects: A Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Contributions of neuroimmune and gut-brain signaling to vulnerability of developing substance use disorders.Neuropharmacology · 2021Review
- Methadone effectively attenuates acute and long-term consequences of neonatal repetitive procedural pain in a rat model.Pediatric research · 2021Article
- Mu and Delta Opioid Receptors Are Coexpressed and Functionally Interact in the Enteric Nervous System of the Mouse Colon.Cellular and molecular gastroenterology and hepatology · 2020Article
- Toward Directing Opioid Receptor Signaling to Refine Opioid Therapeutics.Biological psychiatry · 2020Review
- Methadone Suppresses Neuronal Function and Maturation in Human Cortical Organoids.Frontiers in neuroscience · 2020Article
- A potential role for the gut microbiome in substance use disorders.Psychopharmacology · 2019Review
- Ethanol Reversal of Oxycodone Tolerance in Dorsal Root Ganglia Neurons.Molecular pharmacology · 2018Article
- Tolerance to Morphine-Induced Inhibition of TTX-R Sodium Channels in Dorsal Root Ganglia Neurons Is Modulated by Gut-Derived Mediators.iScience · 2018Article
- The gut-brain interaction in opioid tolerance.Current opinion in pharmacology · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Gastrointestinal peristalsis is significantly dependent on the enteric nervous system. Constipation due to reduced peristalsis is a major side-effect of morphine, which limits the chronic usefulness of this excellent pain reliever in man. The ionic basis for the inhibition of enteric neuron excitability by morphine is not well characterized as previous studies have mainly utilized microelectrode recordings from whole mount myenteric plexus preparations in guinea pigs. Here we have developed a Swiss-Webster mouse myenteric neuron culture and examined their electrophysiological properties by patch-clamp techniques and determined the mechanism for morphine-induced decrease in neuronal excitability. Isolated neurons in culture were confirmed by immunostaining with pan-neuronal marker, β-III tubulin and two populations were identified by calbindin and calretinin staining. Distinct neuronal populations were further identified based on the presence and absence of an afterhyperpolarization (AHP). Cells with AHP expressed greater density of sodium currents. Morphine (3 µM) significantly reduced the amplitude of the action potential, increased the threshold for spike generation but did not alter the resting membrane potential. The decrease in excitability resulted from inhibition of sodium currents. In the presence of morphine, the steady-state voltage dependence of Na channels was shifted to the left with almost 50% of channels unavailable for activation from hyperpolarized potentials. During prolonged exposure to morphine (two hours), action potentials recovered, indicative of the development of tolerance in single enteric neurons. These results demonstrate the feasibility of isolating mouse myenteric neurons and establish sodium channel inhibition as a mechanism for morphine-induced decrease in neuronal excitability.
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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.