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Urgent
REFLUX ESOPHAGITIS AND ESOPHAGEAL HYPERSENSITIVITY
Overview
You have been treating reflux esophagitis for months, or even years. You have taken all kinds of acid-reducing medications, changed your diet, and avoided coffee, alcohol, spicy foods, and hot foods… yet the burning sensation behind your breastbone, chest pain, or esophageal discomfort has still not improved significantly.
If you are also in this situation, the cause may no longer lie in the amount of acid in your stomach. Instead, your esophagus may have become hypersensitive, meaning that even a very small amount of acid, or completely normal stimuli, is enough to cause pain and discomfort.
This condition is known as esophageal hypersensitivity. It is an increasingly recognized cause in patients who still experience reflux symptoms despite adequate and proper treatment with acid-suppressive medications. A proper understanding of this medical condition will help patients avoid unnecessary prolonged use or dose escalation of medication, while enabling the selection of more appropriate treatment modalities.
What is esophageal hypersensitivity?
According to Dr. Mai Vien Phuong, Master’s Degree, Head of the Gastrointestinal Endoscopy Unit at the American International Hospital (AIH), esophageal hypersensitivity is a condition in which nerve endings in the esophageal wall or the central nervous system overreact to stimuli that would not cause discomfort or would only cause very mild sensations in normal individuals. Consequently, patients may experience symptoms such as retrosternal burning, non-cardiac chest pain, or a sensation of a lump or discomfort in the esophagus even in the absence of significant physical lesions or when the level of stimulation is extremely minimal.
In other words, the issue does not lie in the esophagus being exposed to an excessive amount of acid or irritants, but rather in the nervous system that perceives these stimuli becoming overly sensitive.
Mechanisms of esophageal hypersensitivity
Under normal conditions, the esophagus is continuously exposed to various stimuli, such as:
A small amount of acidic or non-acidic refluxate from the stomach.
Distension of the esophageal wall during the swallowing of food or liquids.
Slight changes in the temperature or chemical composition of food.
In healthy individuals, these stimuli typically do not cause any symptoms. However, in people with esophageal hypersensitivity, the same level of stimulation is perceived by the nervous system as pain or discomfort. This is similar to having a “lowered pain perception threshold,” causing the esophagus to overreact to stimuli that would normally be considered insignificant.
Pathogenesis
Currently, esophageal hypersensitivity is considered to be the result of a combination of multiple mechanisms.
1. Peripheral sensitization
Nerve endings located within the esophageal mucosa become more sensitive following prolonged exposure to acid, bile, or inflammatory substances. These repeated stimuli lower the activation threshold of sensory receptors, meaning that even a very small amount of acid or a physiological reflux episode is enough to trigger symptoms.
2. Central sensitization
Not only do the nerve endings in the esophagus change, but the processing of pain signals in the spinal cord and brain is also altered. The brain amplifies the signals from the esophagus, making the patient perceive symptoms much more clearly than the actual stimulus.
This is the same mechanism observed in many other chronic pain disorders such as irritable bowel syndrome, fibromyalgia, or chronic pelvic pain.
3. Mucosal barrier dysfunction
Some studies indicate that the intercellular spaces of the esophageal epithelium may be widened (Dilated Intercellular Spaces), thereby increasing mucosal permeability. Consequently, hydrogen ions (H+), pepsin, or other components of the refluxate can penetrate deeper into the mucosal layer and stimulate nerve endings.
4. Psychological factors
Anxiety, prolonged stress, insomnia, or depression are not direct causes of the condition, but they can increase the perception of pain. These factors affect the brain–gut axis, causing the brain to process signals from the esophagus in a more sensitive manner.
Esophageal Hypersensitivity and Gastroesophageal Reflux Disease
Dr. Mai Vien Phuong, Master’s Degree, explains that these two conditions are related but not entirely the same.
In patients with typical gastroesophageal reflux disease (GERD), symptoms primarily result from excessive exposure of the esophagus to acid. In contrast, in esophageal hypersensitivity, the amount of acid exposure may be completely normal, yet patients still experience symptoms because their pain perception threshold is lowered.
According to the Rome IV criteria, a group of patients is diagnosed with Reflux Hypersensitivity when:
Esophageal endoscopy is normal or shows no significant lesions.
Acid exposure time is within the normal range.
There is a clear association between reflux episodes and the onset of symptoms during 24-hour esophageal pH-impedance monitoring.
If acid exposure time is normal and the symptoms are not associated with reflux episodes, the patient is generally classified as having Functional Heartburn.
Clinical Manifestations
Patients may experience one or more of the following symptoms:
Retrosternal burning.
Non-cardiac chest pain.
A burning or hot sensation radiating up into the throat.
Discomfort after eating.
Symptoms may persist despite treatment with proton pump inhibitors (PPIs).
A key characteristic is that the severity of symptoms is often disproportionate to the findings on endoscopy or other objective tests.
Significance in clinical practice
Recognizing esophageal hypersensitivity is important because not every case of persistent symptoms after PPI therapy is due to inadequate acid control. In many patients, the primary cause is increased sensitivity of the sensory nervous system.
Therefore, continuing to increase the PPI dose or prolonging the duration of PPI use often provides limited benefit. Once other causes have been excluded and the diagnosis has been established, treatment should focus on modulating pain perception with neuromodulators, combined with patient education, lifestyle modifications, and psychological interventions when appropriate.
Esophageal hypersensitivity is a condition characterized by a lowered pain perception threshold in the esophagus, resulting from a combination of peripheral sensitization, central sensitization, mucosal barrier dysfunction, and psychological factors. Patients may experience typical GERD symptoms even when the degree of reflux is not increased or is entirely normal. Proper recognition of this condition helps avoid unnecessary use of acid-suppressive medications and allows for more appropriate treatment, focusing on modulating pain perception and improving quality of life.
Not every case of persistent retrosternal burning or esophageal discomfort is caused by excessive gastric acid secretion. In fact, many patients continue to experience symptoms despite receiving adequate and appropriate treatment with acid-suppressive medications. In such cases, esophageal hypersensitivity should be considered, a condition that can closely resemble gastroesophageal reflux disease in its clinical presentation, but mechanism and treatment approach are totally different.
At the Department of Gastroenterology and Endoscopy, American International Hospital (AIH), equipped with a new-generation Olympus high-definition endoscopy system, physicians can detect esophageal lesions at an early stage while also comprehensively evaluating the underlying causes of persistent esophageal symptoms.
In particular, with clinical experience in gastroenterology, physicians can help distinguish between gastroesophageal reflux disease (GERD) and esophageal hypersensitivity, thereby developing an appropriate treatment plan for each patient and avoiding unnecessary long-term medication use or overlooking the underlying cause of the symptoms.
If you are experiencing persistent retrosternal burning, chest pain, esophageal discomfort, or reflux symptoms that have not improved despite treatment, consulting a gastroenterologist can help accurately identify the underlying cause, assess the severity of the condition, and develop an appropriate treatment plan, thereby effectively controlling symptoms and reducing the risk of complications.
References
aSwada A, Sifrim D, Fujiwara Y. Esophageal Reflux Hypersensitivity: A Comprehensive Review. Gut Liver. 2023;17(6):831-842. doi:10.5009/gnl220373. PMID: 36588526; PMCID: PMC10651372.
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