Role of Esophageal Mast Cell Activation in Noncardiac Chest Pain (NCCP)
Role of Esophageal Mast Cell Activation in Noncardiac Chest Pain (NCCP)
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.
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.
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.