What is the appropriate diagnostic work‑up and management for functional esophageal pain?

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Functional Oesophageal Pain: Diagnostic Work-Up and Management

For functional oesophageal pain, begin with low-dose tricyclic antidepressants or SSRIs as pain modulators after excluding structural disease and GERD through endoscopy with biopsies and ambulatory pH monitoring. 1

Diagnostic Algorithm

Step 1: Exclude Structural and Motility Disorders

Perform upper endoscopy with multiple biopsies (at least 5-6 specimens) from both proximal and distal oesophagus, even if mucosa appears normal, to exclude eosinophilic oesophagitis, malignancy, strictures, and inflammatory conditions. 1, 2, 3 This is critical because eosinophilic oesophagitis can present with normal-appearing mucosa and affects up to 58% of adults with chest pain. 3

Obtain high-resolution manometry to localize the lower oesophageal sphincter, evaluate peristaltic function, and diagnose subtle presentations of achalasia or distal oesophageal spasm that may masquerade as functional pain. 1, 2 High-resolution manometry has superior sensitivity to conventional manometry for recognizing atypical motor disorders. 1, 2

Step 2: Rule Out GERD

Perform ambulatory impedance-pH monitoring off PPI therapy for 7 days if symptoms persist after twice-daily PPI trial and endoscopy is normal. 1 Wireless pH monitoring has superior sensitivity to catheter studies due to extended 48-hour recording. 1

A biphasic oesophagram can complement functional testing, with 80-89% sensitivity and 79-91% specificity for detecting motility disorders, and may reveal dysmotility not seen on manometry. 1, 2

Step 3: Confirm Functional Diagnosis

Functional oesophageal pain is diagnosed when patients have normal manometry, normal oesophageal acid exposure, and negative symptom association after complete oesophageal function testing. 1 The underlying pathophysiology involves oesophageal hypersensitivity from altered pain perception, subtle motor abnormalities, and psychological factors. 1, 4

Management Strategy

First-Line Pharmacological Treatment

Initiate low-dose tricyclic antidepressants (e.g., amitriptyline 10-25 mg at bedtime) or SSRIs as neuromodulators to address altered oesophageal/visceral pain perception, which is the main pathophysiology. 1, 2 Antidepressants increase oesophageal pain thresholds by 7-37% and reduce functional chest pain by 18-67%. 5

Consider a trial of twice-daily PPI therapy if there is any overlap with reflux-like symptoms, as some patients with functional heartburn may have subtle acid sensitivity. 1, 2

Avoid metoclopramide entirely as it is ineffective and potential harms outweigh benefits. 2

Adjunctive Non-Pharmacological Therapies

Cognitive behavioural therapy, oesophageal-directed hypnotherapy, and diaphragmatic breathing exercises can be effective for patients with associated hypervigilance or hypersensitivity. 2, 3 Relaxation training has been shown to reduce symptom scores and oesophageal acid exposure. 1

Abdominal breathing exercises have been reported to improve quality of life scores in patients with oesophageal symptoms. 1

Refractory Cases

For patients not responding to neuromodulators and behavioural therapy, consider baclofen (GABA-B agonist) if regurgitation or belch-predominant symptoms are present, though CNS and GI side effects can occur. 2

Surgical intervention is NOT indicated for functional oesophageal pain, as high-quality evidence for anti-reflux surgery exists only for esophagitis and/or excessive distal oesophageal acid exposure. 1

Critical Pitfalls to Avoid

Never attribute chest pain to oesophageal origin without first completing cardiac evaluation, as the morbidity and mortality of ischemic heart disease substantially exceeds that of oesophageal disorders. 2, 3 Cardiac causes must be excluded first. 2

Do not skip biopsies during endoscopy even with normal-appearing mucosa, as eosinophilic oesophagitis can be latent and present in up to 9% of patients with dysphagia. 2, 3

Recognize that symptom response to PPI is usually poor in functional heartburn (in contrast to GERD), so prolonged empirical PPI therapy without diagnostic confirmation wastes time and resources. 1

Do not rely on a single diagnostic test—barium studies and manometry are complementary, and one may reveal abnormalities missed by the other. 2

Address psychological comorbidities explicitly, as anxiety, panic disorder, depression, and somatoform disorders frequently contribute to persistent symptoms and require specific management. 3, 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Esophageal Spasms: Clinical Description and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Dysphagia or Chest Pain with Negative Esophageal Motility Test

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Effects of antidepressants in patients with functional esophageal disorders or gastroesophageal reflux disease: a systematic review.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2015

Research

Established and Emerging Treatment Options for Functional Heartburn and Chest Pain.

Current treatment options in gastroenterology, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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