# Radiofrequency ablation reduces esophageal hypersensitivity in refractory non-erosive reflux disease

**Authors:** Yan Chen, Xin Lu, Ming Cheng, Mingrui Cui, Xuejun Wen, Kai Mu, Ping Wang, Ying-Jian Zhang

PMC · DOI: 10.3389/fmed.2026.1687564 · Frontiers in Medicine · 2026-02-13

## TL;DR

Radiofrequency ablation helps reduce symptoms in patients with non-erosive reflux disease by lowering esophageal sensitivity and inflammation.

## Contribution

This study shows RFA reduces esophageal hypersensitivity in rNERD via PAR2/TRPV1 pathway modulation.

## Key findings

- RFA significantly reduced PAR2 and TRPV1 expression in rNERD patients.
- Symptom improvement correlated with decreased receptor expression and inflammation.
- RFA alleviates rNERD through anatomical correction and hypersensitivity modulation.

## Abstract

Refractory non-erosive gastroesophageal reflux disease (rNERD) involves complex interactions between esophageal sensitivity receptors (PAR2/TRPV1) and persistent proton pump inhibitor (PPI)-refractory symptoms. This study exclusively employed radiofrequency ablation (RFA) as the uniform endoscopic intervention. All 20 enrolled rNERD patients underwent standardized RFA procedures; no participants underwent mucosal resection or ligation procedures. Post-intervention analysis demonstrated significant reductions in PAR2/TRPV1 expression (PAR2: 81.8% → 35.5%; TRPV1: 1.6 → 0.9 by Western blot) and inflammatory infiltration. Symptom improvement correlated with receptor downregulation (Reflux Symptom Index (RSI): 14.6 → 5.0; Gastroesophageal Reflux Disease Questionnaire (GERD-Q): 14.0 → 7.6). These findings indicate that endoscopic RFA alleviates rNERD symptoms through dual mechanisms: anatomical correction and esophageal hypersensitivity modulation via PAR2/TRPV1 pathways.

## Linked entities

- **Proteins:** F2RL1 (F2R like trypsin receptor 1), TRPV1 (transient receptor potential cation channel subfamily V member 1)
- **Diseases:** gastroesophageal reflux disease (MONDO:0007186)

## Full-text entities

- **Genes:** IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, TRPV1 (transient receptor potential cation channel subfamily V member 1) [NCBI Gene 7442] {aka VR1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, BLNK (B cell linker) [NCBI Gene 29760] {aka AGM4, BASH, BLNK-S, LY57, SLP-65, SLP65}, ASIC3 (acid sensing ion channel subunit 3) [NCBI Gene 9311] {aka ACCN3, DRASIC, SLNAC1, TNaC1}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}, F2RL1 (F2R like trypsin receptor 1) [NCBI Gene 2150] {aka GPR11, PAR2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, PCLAF (PCNA clamp associated factor) [NCBI Gene 9768] {aka KIAA0101, L5, NS5ATP9, OEATC, OEATC-1, OEATC1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, TAC1 (tachykinin precursor 1) [NCBI Gene 6863] {aka Hs.2563, NK2, NKNA, NPK, TAC2}
- **Diseases:** liver and kidney diseases (MESH:D008107), globus pharyngeus (MESH:D000079564), Esophageal inflammation (MESH:D007249), gastroesophageal reflux (MESH:D005764), malignant tumor (MESH:D009369), diabetes and other diseases (MESH:D003920), heart and lung diseases (MESH:D008171), anxiety (MESH:D001007), asthma (MESH:D001249), achalasia (MESH:D004931), obesity (MESH:D009765), throat discomfort (MESH:C538390), chest pain (MESH:D002637), refractory (MESH:D000069279), esophageal dysmotility (MESH:D015154), hypotensive (MESH:D007022), obstruction (MESH:D000402), food reflux (MESH:D005517), acid regurgitation (MESH:D008944), esophagitis (MESH:D004941), motility defects (MESH:D015835), esophageal hypersensitivity (MESH:D004935), upper gastrointestinal disorders (MESH:D005767), chronic cough (MESH:D003371), NERD (MESH:D014077), ulcer (MESH:D014456), mucosal damage (MESH:D052016), depression (MESH:D003866), abdominal distension (MESH:D000007), heartburn (MESH:D006356), VH (MESH:D004342), constipation (MESH:D003248), bloating (MESH:C535647)
- **Chemicals:** paraffin (MESH:D010232), carbonate (MESH:D002254), 5'-iodoresiniferatoxin (MESH:C468130), acid (MESH:D000143), xylene (MESH:D014992), water (MESH:D014867), famotidine (MESH:D015738), tetrodotoxin (MESH:D013779), SDS (MESH:D012967), ethanol (MESH:D000431), AA (-), hydrogen peroxide (MESH:D006861), HE (MESH:D006371), hematoxylin (MESH:D006416), omeprazole (MESH:D009853), polystyrene (MESH:D011137), citrate (MESH:D019343), capsaicin (MESH:D002211), PBS (MESH:D007854), 3,3'-diaminobenzidine (MESH:D015100), eosin (MESH:D004801), hydrogen (MESH:D006859), PVDF (MESH:C024865), alcohol (MESH:D000438), formaldehyde (MESH:D005557), sulfuric acid (MESH:C033158)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** P0010S

## Full text

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## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12947267/full.md

## References

57 references — full list in the complete paper: https://tomesphere.com/paper/PMC12947267/full.md

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Source: https://tomesphere.com/paper/PMC12947267