Neurocognitive processing of esophageal central sensitization in the insula and cingulate gyrus.
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.
Lawal
Adeyemi
A
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Kern
Mark
M
Sanjeevi
Arthi
A
Antonik
Stephen
S
Mepani
Rachel
R
Rittmann
Tanya
T
Hussaini
Syed
S
Hofmann
Candy
C
Tatro
Linda
L
Jesmanowicz
Andrzej
A
Verber
Matt
M
Shaker
Reza
R
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
D006851:Hydrochloric Acid