Immune-mediated neural dysfunction in a murine model of chronic Helicobacter pylori infection

Přemysl Berčík, Roberto De Giorgio, Patricia Blennerhassett, Elena F. Verdú, Giovanni Barbara, Stephen M. Collins

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background & Aims: Neuromuscular changes producing dysmotility and hyperalgesia may underlie symptom generation in functional gastrointestinal disorders. We investigated whether chronic Helicobacter pylori-induced gastritis causes neuromuscular dysfunction. Methods: In vitro muscle contractility and acetylcholine release were evaluated in mice before and after H. pylori eradication. H. pylori colonization and gastritis were graded histologically. Substance P (SP)-, vasoactive intestinal polypeptide (VIP)-, and calcitonin gene-related peptide (CGRP) immunoreactivity (IR) and macrophages were studied by immunohistochemistry. Results: In Balb/c mice, chronic H. pylori infection did not affect muscle function but augmented antral relaxation after nerve electric field stimulation. Infected mice had lower acetylcholine release by electric field stimulation and had higher density of SP-, CGRP-, and VIP-IR nerves in the stomach and of SP- and CGRP-IR in the spinal cord. Cholinergic nerve dysfunction worsened progressively and was associated with increasing macrophage and mononuclear but not polymorphonuclear infiltrate or bacterial colonization. SCID mice had unchanged acetylcholine release despite high H. pylori colonization and macrophage infiltration. Eradication of H. pylori normalized functional and morphologic abnormalities except for increased density of gastric SP- and CGRP-IR nerves. Conclusions: H. pylori infection induces functional and morphologic changes in the gastric neural circuitry that are progressive and lymphocyte dependent, and some persist after H. pylori eradication. The data have direct implications regarding the role of H. pylori infection in functional dyspepsia.
    Original languageEnglish
    Pages (from-to)1205-1215
    Number of pages10
    JournalGastroenterology
    Volume123
    Issue number4
    DOIs
    Publication statusPublished - 1 Oct 2002

    Keywords

    • metabolism: Acetylcholine
    • Animals
    • analysis: Calcitonin Gene-Related Peptide
    • Disease Models, Animal
    • chemistry: Enteric Nervous System
    • Female
    • immunology: Gastritis
    • immunology: Helicobacter Infections
    • Helicobacter pylori
    • Immunohistochemistry
    • immunology: Macrophages
    • Mice
    • Mice, Inbred BALB C
    • Mice, SCID
    • physiology: Muscle Contraction
    • Specific Pathogen-Free Organisms
    • chemistry: Spinal Cord
    • innervation: Stomach
    • analysis: Substance P
    • analysis: Vasoactive Intestinal Peptide

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