title: Neurocognitive processing of esophageal central sensitization in the insula and cingulate gyrus.
abstract: 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 mm(3) 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.
authors.affiliation: Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Adeyemi
authors.initials: A
authors.lastname: Lawal
authors.forename: Mark
authors.initials: M
authors.lastname: Kern
authors.forename: Arthi
authors.initials: A
authors.lastname: Sanjeevi
authors.forename: Stephen
authors.initials: S
authors.lastname: Antonik
authors.forename: Rachel
authors.initials: R
authors.lastname: Mepani
authors.forename: Tanya
authors.initials: T
authors.lastname: Rittmann
authors.forename: Syed
authors.initials: S
authors.lastname: Hussaini
authors.forename: Candy
authors.initials: C
authors.lastname: Hofmann
authors.forename: Linda
authors.initials: L
authors.lastname: Tatro
authors.forename: Andrzej
authors.initials: A
authors.lastname: Jesmanowicz
authors.forename: Matt
authors.initials: M
authors.lastname: Verber
authors.forename: Reza
authors.initials: R
authors.lastname: Shaker
mesh_terms: D000293:Adolescent; D000328:Adult; D002404:Catheterization; D002540:Cerebral Cortex / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D004106:Dilatation; D004947:Esophagus / Q000294:innervation* / Q000502:physiology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000502:physiology*; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D010812:Physical Stimulation; D013268:Stimulation, Chemical
chemical_list: D006851:Hydrochloric Acid