Seventy percent of patients coming to the emergency room with chest pain have normal coronary arteries and thus have non-cardiac pain. Esophagus is suspected to be the cause of pain in these patients. Gastro- esophageal reflux and esophageal spasm are 2 possible major causes of esophageal pain. With the availability of potent acid inhibition therapy (proton pump inhibitors) it is possible to treat acid reflux effectiely. However, large number of patients continues to experience chest pain symptoms and come to the medical emergency room frequently. One of the possible causes of chest pain in these patients is esophageal spasm, however large number of studies conducted in 1990's failed to identify abnormal motor event at the time of pain. Current thinking is that esophageal hypersensitivity, central or peripheral, is the cause of pain in these patients. Using simultaneous ultrasound imaging and manometery we found a unique """"""""sustained esophageal contraction (SEC)"""""""" in association with esophageal pain and heartburn in the late 90's. The SEC was later determined to be actually a prolonged contraction of the longitudinal muscles of the esophagus and thus could not be recorded by intraluminal manometry. During last funding period, we have made number of observations with regards to the role of longitudinal muscles of the esophagus in health and disease. One of the problems is that recording of longitudinal muscle contraction with US imaging, especially over extended periods of time in humans, is quite tedious. Other laboratories have not made an attempt to study longitudinal muscle spasm and its relationship with esophageal pain, thereby preventing wide acceptance of our observations. High resolution manometry is a relatively novel technique to record contraction of the circular muscles of esophagus at closely spaced intervals. Our observations suggest that HRM can also record longitudinal muscle contraction related esophageal shortening of the esophagus. The goals of our study are;1) to determine the temporal correlation between esophageal pain/heartburn and longitudinal muscle spasm of the esophagus using a novel form of HRM, i.e., ambulatory HRM. The latter can be performed for extended periods of time and thus making it possible to determine the temporal correlation between spontaneous pain and motor events. How does longitudinal muscle spasm cause pain? We propose that muscle spasm induces ischemia of the wall of the esophagus. 2) Using Laser Doppler technique we plan to study the effects of muscle contraction on the blood flow in the wall of esophagus in the animal experiments. 3) Finally, we will determine the temporal correlation between longitudinal muscle spasm, esophageal wall ischemia and non cardiac or esophageal pain. With the better understanding of pathogenesis of pain, we hope more effective strategies to treat esophageal pain will be forthcoming.

Public Health Relevance

Our preliminary studies show that esophageal wall ischemia related to prolonged contraction of the longitudinal muscles of the esophagus is temporally related to esophageal pain/heartburn. We use novel technique of ambulatory high resolution manometry to demonstrate the temporal correlation between esophageal pain and longitudinal muscle spasm. Laser Doppler technique is used to study the effects of esophageal contractions on the esophageal blood flow to demonstrate temporal correlation between esophageal pain and esophageal wall ischemia in humans.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Clinical, Integrative and Molecular Gastroenterology Study Section (CIMG)
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Hamilton, Frank A
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University of California San Diego
Internal Medicine/Medicine
Schools of Medicine
La Jolla
United States
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Mittal, Ravinder K (2018) Is the Lower Esophageal Sphincter Tone Related to a Gas? Cell Mol Gastroenterol Hepatol 5:239-240
Zifan, Ali; Sun, Catherine; Gourcerol, Guillaume et al. (2018) Endoflip vs high-definition manometry in the assessment of fecal incontinence: A data-driven unsupervised comparison. Neurogastroenterol Motil 30:e13462
Babaei, Arash; Mittal, Ravinder (2018) Cholecystokinin induces esophageal longitudinal muscle contraction and transient lower esophageal sphincter relaxation in healthy humans. Am J Physiol Gastrointest Liver Physiol 315:G734-G742
Park, Subum; Zifan, Ali; Kumar, Dushyant et al. (2018) Genesis of Esophageal Pressurization and Bolus Flow Patterns in Patients With Achalasia Esophagus. Gastroenterology 155:327-336
Zifan, A; Jiang, Y; Mittal, R K (2017) Temporal and spectral properties of esophageal mucosal blood perfusion: a comparison between normal subjects and nutcracker esophagus patients. Neurogastroenterol Motil 29:
Zifan, Ali; Kumar, Dushyant; Cheng, Leo K et al. (2017) Three-Dimensional Myoarchitecture of the Lower Esophageal Sphincter and Esophageal Hiatus Using Optical Sectioning Microscopy. Sci Rep 7:13188
Mittal, Ravinder K; Zifan, Ali; Kumar, Dushyant et al. (2017) Functional morphology of the lower esophageal sphincter and crural diaphragm determined by three-dimensional high-resolution esophago-gastric junction pressure profile and CT imaging. Am J Physiol Gastrointest Liver Physiol 313:G212-G219
Jiang, Yanfen; Mittal, Ravinder K (2016) Low esophageal mucosal blood flow in patients with nutcracker esophagus. Am J Physiol Gastrointest Liver Physiol 310:G410-6
Lee, Robert H; Korsapati, Hariprasad; Bhalla, Vikas et al. (2016) Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects. J Neurogastroenterol Motil 22:436-43
Patel, Nirali; Jiang, Yanfen; Mittal, Ravinder K et al. (2015) Circular and longitudinal muscles shortening indicates sliding patterns during peristalsis and transient lower esophageal sphincter relaxation. Am J Physiol Gastrointest Liver Physiol 309:G360-7

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