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Am J Physiol Gastrointest Liver Physiol 294: G787-G794, 2008. First published January 10, 2008; doi:10.1152/ajpgi.00421.2007
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NEUROREGULATION AND MOTILITY

Neurocognitive processing of esophageal central sensitization in the insula and cingulate gyrus

Adeyemi Lawal,1 Mark Kern,1 Arthi Sanjeevi,1 Stephen Antonik,1 Rachel Mepani,1 Tanya Rittmann,1 Syed Hussaini,1 Candy Hofmann,1 Linda Tatro,1 Andrzej Jesmanowicz,2 Matt Verber,2 and Reza Shaker1

1Division of Gastroenterology and Hepatology and 2Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 18 September 2007 ; accepted in final form 6 January 2008

The cingulate and insular cortices are parts of the limbic system that process and modulate gastrointestinal sensory signals. We hypothesized that sensitization of these two limbic area may operate in esophageal sensitization. Thus the objective of the study was to elucidate the neurocognitive processing in the cingulate and insular cortices to mechanical stimulation of the proximal esophagus following infusion of acid or phosphate buffer solution (PBS) into the esophagus. Twenty-six studies (14 to acid and 12 to PBS infusion) were performed in 20 healthy subjects (18–35 yr) using high-resolution (2.5 x 2.5 x 2.5 mm3 voxel size) functional MRI (fMRI). Paradigm-driven, 2-min fMRI scans were performed during randomly timed 15-s intervals of proximal esophageal barostatically controlled distentions and rest, before and after 30-min of distal esophageal acid or PBS perfusion (0.1 N HCl or 0.1 M PBS at 1 ml/min). Following distal esophageal acid infusion, at subliminal and liminal levels of proximal esophageal distentions, the number of activated voxels in both cingulate and insular cortices showed a significant increase compared with before acid infusion (P < 0.05). No statistically significant change in cortical activity was noted following PBS infusion. We conclude that 1) acid stimulation of the esophagus results in sensitization of the cingulate and insular cortices to subliminal and liminal nonpainful mechanical stimulations, and 2) these findings can have ramifications with regard to the mechanisms of some esophageal symptoms attributed to reflux disease.

reflux disease; esophageal distension; fMRI; hypersensitivity; esophageal acid stimulation



Address for reprint requests and other correspondence: R. Shaker, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 W. Wisconsin Ave., Milwaukee, WI 53226 (e-mail: rshaker{at}mcw.edu)




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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Kern, K. Chai, A. Lawal, and R. Shaker
Effect of esophageal acid exposure on the cortical swallowing network in healthy human subjects
Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G152 - G158.
[Abstract] [Full Text] [PDF]




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