Role of Esophageal Mast Cell Activation in Noncardiac Chest Pain (NCCP)
| Status: | Completed |
|---|---|
| Conditions: | Angina |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/2/2016 |
| Start Date: | September 2005 |
| End Date: | September 2008 |
| Contact: | Shaouyong Yu, MD, MPH |
| Email: | suy13@psu.edu |
| Phone: | 717-531-4466 |
Chest pain is a common clinical complaint. About 30% patients with chest pain will have a
normal coronary angiogram and are described as having noncardiac chest pain (NCCP). It is
estimated that 25% of the population complain of chest pain at some time in their lifetime.
The pathogenesis of NCCP is unknown. Esophageal hypersensitivity as a result of inflammation
is considered to be an important mechanism in the development of this pain sensation. Little
is currently known about the interaction between inflammatory mediators and peripheral
afferent nerve terminals in the esophagus. The mast cell is one of the most enriched
pro-inflammatory cells in the gastrointestinal tract. Activation of the mucosal mast cell
releases a variety of mediators into adjacent tissues. We hypothesize that mediators
released by mast cells sensitize esophageal nociceptors and induce pain sensation.
normal coronary angiogram and are described as having noncardiac chest pain (NCCP). It is
estimated that 25% of the population complain of chest pain at some time in their lifetime.
The pathogenesis of NCCP is unknown. Esophageal hypersensitivity as a result of inflammation
is considered to be an important mechanism in the development of this pain sensation. Little
is currently known about the interaction between inflammatory mediators and peripheral
afferent nerve terminals in the esophagus. The mast cell is one of the most enriched
pro-inflammatory cells in the gastrointestinal tract. Activation of the mucosal mast cell
releases a variety of mediators into adjacent tissues. We hypothesize that mediators
released by mast cells sensitize esophageal nociceptors and induce pain sensation.
1. Key Objectives: To determine the density and activation of esophageal mast cells in
non-cardiac chest pain patients. We expect to find mast cell activation, as measured by
mast cell count or degranluation, tryptase staining, and histamine release, will be
greater in NCCP patients compared to controls, and the increased mast cell activation
will correlate with the severity of NCCP. These results will expand our understanding
of the pathogenesis of esophageal originated NCCP, and allow the development of new
diagnostic and treatment options.
2. Study Population: (i) NCCP (ii) Reflux esophagitis (iii) Control subjects.
3. Summary of Procedures: (i) symptom assessment by chest pain questionnaire; (ii)
esophageal reflux evaluation by review of records of 24-hour pH monitoring; (iii)
evidence of esophagitis by endoscopy; (iv) esophageal biopsy by endoscopy; (v) mast
cell activation study in biopsy specimen by mast cell count, tryptase and Transient
receptor potential vanniloid-1 (TRPV1) staining, and histamine release assay.
4. Major Risks & Discomforts: There are no major risks & discomforts other than involved
in standard upper GI endoscopy.
non-cardiac chest pain patients. We expect to find mast cell activation, as measured by
mast cell count or degranluation, tryptase staining, and histamine release, will be
greater in NCCP patients compared to controls, and the increased mast cell activation
will correlate with the severity of NCCP. These results will expand our understanding
of the pathogenesis of esophageal originated NCCP, and allow the development of new
diagnostic and treatment options.
2. Study Population: (i) NCCP (ii) Reflux esophagitis (iii) Control subjects.
3. Summary of Procedures: (i) symptom assessment by chest pain questionnaire; (ii)
esophageal reflux evaluation by review of records of 24-hour pH monitoring; (iii)
evidence of esophagitis by endoscopy; (iv) esophageal biopsy by endoscopy; (v) mast
cell activation study in biopsy specimen by mast cell count, tryptase and Transient
receptor potential vanniloid-1 (TRPV1) staining, and histamine release assay.
4. Major Risks & Discomforts: There are no major risks & discomforts other than involved
in standard upper GI endoscopy.
Inclusion Criteria:
- NCCP – presence of a history of chest pain with a negative cardiac evaluation, no
evidence of gross esophagitis on endoscopy, and lack of any exclusion criteria;
Reflux esophagitis – presence of chest pain or heartburn, negative cardiac
evaluation, lack of exclusion criteria and presence of esophagitis on endoscopy;
- Controls – lack of history of chest pain, lack of exclusion criteria and lack of
esophagitis on endoscopy. It is anticipated that patients being evaluated for heme
positive stool or GI bleeding would be included as controls.
Exclusion Criteria:
- History of ischemic heart disease, history of asthma, significant food allergies, celiac
disease, chronic inflammatory conditions (SLE, rheumatoid arthritis), atopic skin disease,
varices, coagulopathy, recent drug treatment with steroids.
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