Evidence map›Paper›PMID 35106734›Full record

ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2022

Chronic Morphine Induces IL-18 in Ileum Myenteric Plexus Neurons Through Mu-opioid Receptor Activation in Cholinergic and VIPergic Neurons.

Karan H Muchhala, Eda Koseli, Aravind R Gade, Kareem Woods, Suha Minai, Minho Kang, A Rory McQuiston, William L Dewey, Hamid I Akbarali

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. 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 · 2024
    Article
  5. 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

9 authors at 1 institution in 1 country.

Karan H MuchhalaDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 1112 E. Clay Street, Richmond, VA, 23298, USA.
Eda KoseliDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 1112 E. Clay Street, Richmond, VA, 23298, USA.
Aravind R GadeDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 1112 E. Clay Street, Richmond, VA, 23298, USA.
Kareem WoodsDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 1112 E. Clay Street, Richmond, VA, 23298, USA.
Suha MinaiDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 1112 E. Clay Street, Richmond, VA, 23298, USA.
Minho KangDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 1112 E. Clay Street, Richmond, VA, 23298, USA.
A Rory McQuistonDepartment of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA, 23298, USA.
William L DeweyDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 1112 E. Clay Street, Richmond, VA, 23298, USA.
Hamid I AkbaraliDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 1112 E. Clay Street, Richmond, VA, 23298, USA. Hamid.akbarali@vcuhealth.org.ORCID 0000-0003-1423-0774
Virginia Commonwealth University · US

Funding

VCU Center for Drug Addiction ResearchP30DA033934 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI Matthew Sean Halquist · 2014 to 2026
$13.8M
Virginia Commonwealth University Initiative for Maximizing Student DevelopmentR25GM090084 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI AKBARALI, HAMID I, LLOYD, JOYCE A. · 2010 to 2022
$5.2M
Mechanisms of Ethanol's Reversal of Opioid ToleranceR01DA036975 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI AKBARALI, HAMID I, DEWEY, WILLIAM L. · 2014 to 2018
$2.3M
NIDA NIH HHS P30 DA033934NIDA NIH HHS R01 DA036975NIGMS NIH HHS R25 GM090084NIH HHS DA036975NIH HHS P30DA033934NIH HHS R25GM090084
6 · The paper itself

Abstract

The gastrointestinal epithelium is critical for maintaining a symbiotic relationship with commensal microbiota. Chronic morphine exposure can compromise the gut epithelial barrier in mice and lead to dysbiosis. Recently, studies have implicated morphine-induced dysbiosis in the mechanism of antinociceptive tolerance and reward, suggesting the presence of a gut-brain axis in the pharmacological effects of morphine. However, the mechanism(s) underlying morphine-induced changes in the gut microbiome remains unclear. The pro-inflammatory cytokine, Interleukin-18 (IL-18), released by enteric neurons can modulate gut barrier function. Therefore, in the present study we investigated the effect of morphine on IL-18 expression in the mouse ileum. We observed that chronic morphine exposure in vivo induces IL-18 expression in the ileum myenteric plexus that is attenuated by naloxone. Given that mu-opioid receptors (MORs) are mainly expressed in enteric neurons, we also characterized morphine effects on the excitability of cholinergic (excitatory) and vasoactive intestinal peptide (VIP)-expressing (inhibitory) myenteric neurons. We found fundamental differences in the electrical properties of cholinergic and VIP neurons such that VIP neurons are more excitable than cholinergic neurons. Furthermore, MORs were primarily expressed in cholinergic neurons, although a subset of VIP neurons also expressed MORs and responded to morphine in electrophysiology experiments. In conclusion, these data show that morphine increases IL-18 in ileum myenteric plexus neurons via activation of MORs in a subset of cholinergic and VIP neurons. Thus, understanding the neurochemistry and electrophysiology of MOR-expressing enteric neurons can help to delineate mechanisms by which morphine perturbs the gut barrier.

Indexed as

MorphineMyenteric PlexusAnimalsCholinergic AgentsInterleukin-18MiceReceptors, OpioidCholinergic AgentsInterleukin-18MorphineReceptors, OpioidChronic morphineEnteric neuronsGut epithelial barrierInterleukin-18 (IL-18)Mu-opioid receptorNeurochemical coding

Identifiers

PMID35106734
PMCPMC9343479
OpenAlexW4210529044

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.