Substance P-Related Neuro-Immune-Epithelial Interactions May Play a Role in Mucosal Damage in Gastro-Oesophageal Reflux Disease - Summary - MDSpire

Substance P-Related Neuro-Immune-Epithelial Interactions May Play a Role in Mucosal Damage in Gastro-Oesophageal Reflux Disease

  • By

  • Tom Leech

  • Philip Woodland

  • Madusha Peiris

  • April 27, 2026

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Objective:

To investigate the expression of Substance P receptors in the oesophageal mucosa of healthy controls and GORD patients, including the localization of mast cells in relation to SP+ nerve fibers, and to explore the effects of Substance P on oesophageal epithelial cells.

Approach:
    Key Findings:
    • NK1R expression was significantly higher in NERD and ERD mucosa compared to healthy controls, indicating a potential role in inflammation.
    • Substance P exposure induced NF-κB phosphorylation and cytokine release (IL-6 and IL-8) in NE-1 cells, suggesting a direct inflammatory effect.
    • Density of MRGPRX2+ mast cells was significantly higher in NERD and ERD compared to healthy controls, highlighting their potential role in GORD pathology.
    • A significant proportion of SP+ nerve fibres were located near mast cells, indicating a possible interaction that may influence mucosal inflammation.
    Interpretation:

    The upregulation of SP receptors in GORD patients suggests a role in mucosal inflammation and sensory nerve activation, potentially contributing to the pathophysiology of GORD. These findings align with existing literature on neuro-immune interactions in chronic inflammatory conditions.

    Limitations:
    • The study's sample size was relatively small, which may limit the generalizability of the findings.
    • The findings are based on biopsies and in vitro experiments, which may not fully represent in vivo conditions, and potential biases in sample selection should be considered.
    Conclusion:

    Substance P and its receptors are implicated in the inflammatory processes of GORD, highlighting potential therapeutic targets for managing mucosal damage.

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