Gastroesophageal Reflux Disease (GERD) is the most common malady of the esophagus and affects over 20% of the US population. While mucosal injury in GERD responds adequately to medical therapy, remedying the GERD symptoms such as heartburn and sensation/awareness of the refluxate movement within the esophagus referred to as regurgitation movement especially in the absence of mucosal injury, which comprises nearly half of this patient population, poses a significant clinical challenge. Thi is primarily due to lack of clear understanding of the cerebral cortical mechanisms involved in sensory physiology and pathophysiology of GERD. The current proposal addresses this deficiency at two levels. At the cerebral cortical level in humans it utilizes advance imaging technology to characterize the effect of chronic and acute esophageal acid exposure on local and large scale cortical networks that are involved in visceral sensation, interoception/homeostasis and awareness in healthy individuals and patients with well defined various GERD sub-types including erosive and non erosive reflux disease as well as functional heartburn. The proposed animal studies will delineate the underlying cortical mechanisms of sensory pathophysiology in GERD using an integrated imaging, molecular, and electrophysiological approach. We have focused these studies on two animal models;repeated acid exposure and chronic erosive esophagitis. These resemble non-erosive and erosive reflux in humans. These investigations complement the human studies and will provide in depth insight into the effect of chronic and acute esophageal acid exposure on the cortex, insight that cannot be obtained from humans. The obtained information will increase our understanding of the cortical sensory pathophysiology of GERD and as such has the potential to lead to newer diagnostic and therapeutic modalities and positively impact clinical practice and potentially reduce health care expenditure. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

Public Health Relevance

Gastroeophageal reflux disease (GERD) affects over 20% of the population. Reportedly 7-10% of US population suffers daily from heartburn the cardinal symptom of GERD. Mucosal injury in GERD is easily treated but remedying the symptom of heartburn in the absence of mucosal injury which constitute over half of these patients is a difficult clinical challenge which results in significant burden on the individual and society. Thi shortcoming is in part due to lack of a clear understanding of the brain processing of sensory information from the esophagus. The current proposal addresses this deficiency at two levels. At the whole brain level it will determine the effect of GERD on local and large scale cortical networks that are involved in visceral sensation, interoception/homeostasis and awareness. At the brain receptor level, it will determine how esophageal acid exposure can influence the neuronal receptors and their reaction to stimulation. Findings are anticipated to advance our understanding of the cortical mechanisms in sensory pathophysiology of GERD and help guide development of better diagnosis and therapy. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DK025731-31
Application #
8716728
Study Section
Clinical, Integrative and Molecular Gastroenterology Study Section (CIMG)
Program Officer
Hamilton, Frank A
Project Start
Project End
Budget Start
Budget End
Support Year
31
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Siwiec, R M; Babaei, A; Kern, M et al. (2015) Esophageal acid stimulation alters insular cortex functional connectivity in gastroesophageal reflux disease. Neurogastroenterol Motil 27:201-11
Shaker, Reza; Babaei, Arash; Naini, Sohrab R (2014) Prevention of esophagopharyngeal reflux by augmenting the upper esophageal sphincter pressure barrier. Laryngoscope 124:2268-74
Lang, Ivan M; Medda, Bidyut K; Babaei, Arash et al. (2014) Role of peripheral reflexes in the initiation of the esophageal phase of swallowing. Am J Physiol Gastrointest Liver Physiol 306:G728-37
Dua, Kulwinder S; Surapaneni, Sri Naveen; Kuribayashi, Shiko et al. (2014) Effect of aging on hypopharyngeal safe volume and the aerodigestive reflexes protecting the airways. Laryngoscope 124:1862-8
Babaei, Arash; Ward, B Douglas; Siwiec, Robert M et al. (2013) Functional connectivity of the cortical swallowing network in humans. Neuroimage 76:33-44
Banerjee, B; Medda, B K; Pochiraju, S et al. (2013) AMPA receptor subunits expression and phosphorylation in cingulate cortex in rats following esophageal acid exposure. Neurogastroenterol Motil 25:973-e776
Babaei, A; Siwiec, R M; Kern, M et al. (2013) Intrinsic functional connectivity of the brain swallowing network during subliminal esophageal acid stimulation. Neurogastroenterol Motil 25:992-e779
Lang, I M; Medda, B K; Jadcherla, S et al. (2012) The role of the superior laryngeal nerve in esophageal reflexes. Am J Physiol Gastrointest Liver Physiol 302:G1445-57
Babaei, Arash; Dua, Kulwinder; Naini, Sohrab Rahimi et al. (2012) Response of the upper esophageal sphincter to esophageal distension is affected by posture, velocity, volume, and composition of the infusate. Gastroenterology 142:734-743.e7
Banerjee, Banani; Medda, Bidyut K; Schmidt, Jamie et al. (2011) Neuronal plasticity in the cingulate cortex of rats following esophageal acid exposure in early life. Gastroenterology 141:544-52

Showing the most recent 10 out of 102 publications