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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK060733-10A1
Application #
8295586
Study Section
Clinical, Integrative and Molecular Gastroenterology Study Section (CIMG)
Program Officer
Hamilton, Frank A
Project Start
2001-12-01
Project End
2017-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
10
Fiscal Year
2012
Total Cost
$336,853
Indirect Cost
$119,353
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Kim, J H; Mittal, R K; Patel, N et al. (2014) Esophageal distension during bolus transport: can it be detected by intraluminal impedance recordings? Neurogastroenterol Motil 26:1122-30
Mittal, Ravinder K (2014) Esophageal function testing: beyond manometry and impedance. Gastrointest Endosc Clin N Am 24:667-85
Mittal, Ravinder K (2013) Longitudinal muscle of the esophagus: its role in esophageal health and disease. Curr Opin Gastroenterol 29:421-30
Leslie, Eric; Bhargava, Valmik; Mittal, Ravinder K (2012) A novel pattern of longitudinal muscle contraction with subthreshold pharyngeal stimulus: a possible mechanism of lower esophageal sphincter relaxation. Am J Physiol Gastrointest Liver Physiol 302:G542-7
Mittal, R K; Karstens, A; Leslie, E et al. (2012) Ambulatory high-resolution manometry, lower esophageal sphincter lift and transient lower esophageal sphincter relaxation. Neurogastroenterol Motil 24:40-6, e2
Raizada, V; Bhargava, V; Karsten, A et al. (2011) Functional morphology of anal sphincter complex unveiled by high definition anal manometery and three dimensional ultrasound imaging. Neurogastroenterol Motil 23:1013-9, e460
Babaei, A; Mittal, R K (2011) Cardiovascular compression of the esophagus and spread of gastro-esophageal reflux. Neurogastroenterol Motil 23:45-51, e3
Abrahao Jr, L; Bhargava, V; Babaei, A et al. (2011) Swallow induces a peristaltic wave of distension that marches in front of the peristaltic wave of contraction. Neurogastroenterol Motil 23:201-7, e110
Weinstein, Milena M; Pretorius, Dolores H; Jung, Sung-Ae et al. (2011) Anal sphincter complex muscles defects and dysfunction in asymptomatic parous women. Int Urogynecol J 22:1143-50
Hong, Su Jin; Bhargava, Valmik; Jiang, Yanfen et al. (2010) A unique esophageal motor pattern that involves longitudinal muscles is responsible for emptying in achalasia esophagus. Gastroenterology 139:102-11

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