Substance P-Related Neuro-Immune-Epithelial Interactions in GORD

Overview

This study investigates the role of Substance P (SP) in gastro-oesophageal reflux disease (GORD), highlighting its receptor expression and inflammatory effects on the oesophageal mucosa. Findings suggest that SP may contribute to mucosal damage through neuro-immune interactions.

Background

Gastro-oesophageal reflux disease (GORD) affects a significant portion of the population and is characterized by symptoms such as heartburn, which result from the activation of sensory nerve fibers in the oesophageal mucosa. Understanding the neuro-immune-epithelial interactions in GORD is crucial for developing targeted therapies, particularly as inflammatory markers are upregulated in affected patients.

Data Highlights

Key Findings

• NK1R expression is significantly higher in NERD and ERD compared to healthy controls.
• SP exposure in NE-1 cells induces NF-κB phosphorylation and cytokine release (IL-6 and IL-8).
• The density of MRGPRX2+ mast cells is significantly increased in NERD and ERD mucosa.
• 32% of SP+ nerve fibers are located within 10 µm of a mast cell, indicating close neuro-immune interactions.
• SP may play a role in the pathogenesis of mucosal damage in GORD through inflammatory pathways.

Clinical Implications

The findings suggest that targeting SP receptors, particularly NK1R and MRGPRX2, may offer new therapeutic avenues for managing GORD. Understanding the inflammatory pathways activated by SP could lead to more effective treatments for patients with NERD and ERD.

Conclusion

Substance P and its receptors are implicated in the inflammatory processes of GORD, highlighting the importance of neuro-immune interactions in the disease's pathophysiology. Further research may elucidate potential therapeutic targets.

References

1. Journal of Gastroenterology, 2023 -- Neuroimmune Interactions in the Mucosa and Their Role in the Development of Gastro-Oesophageal Reflux Disease (GORD)
2. Journal of Gastroenterology, 2019 -- Eosinophilic Esophagitis: Emerging Insights into Its Pathophysiology and Clinical Features
3. Journal of Gastroenterology, 2023 -- Exploring the Role of Epigenetics in the Pathophysiology of Irritable Bowel Syndrome
4. Journal of Gastroenterology — Interactions Between Epithelial and Stromal Components in Eosinophilic Esophagitis-Related Fibrosis
5. ASGE | American Society for Gastrointestinal Endoscopy guideline on the diagnosis and management of GERD: summary and recommendations
6. Dose and duration shape the efficacy of vonoprazan versus lansoprazole for erosive esophagitis: insights from meta-regression - PMC
7. Immune functions of the esophagus - PubMed