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 ϫ 2.5 ϫ 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 Ͻ 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 GASTROESOPHAGEAL REFLUX EVENTS result in both chemical and mechanical stimulation of the esophagus by acid and distention, respectively. It is conceivable that chemical stimulation of the distal esophagus results in sensitization of the proximal esophagus to the distention component of the reflux event through the process of central sensitization and facilitates the development of distention-related symptoms even in the absence of the chemical component of the refluxate.Visceral hypersensitivity is thought to contribute to functional esophageal pain, and this is believed to be due to a complex interaction between peripheral and spinal nerves, higher cortical centers, descending inhibitory pathway, and psychological modulation triggered by the stimulus (14, 25). Various attempts have been made to elucidate the mechanisms of the exaggerated visceral sensitivity in humans using various neurophysiological and brain imaging techniques. The limbic system, which includes the insular, cingulate, amygdala, thalamus, hypothalamus, and prefrontal cortex has been reported to participate in the processing of esophageal afferent sensory inputs (3,19,22). In particular, the insula and cingulate have been shown to participate in the integration of autonomic, affective, cognitive, and motor responses to sensory signals originating from the upper and lower gastrointestinal tract (11).Al...

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Using dynamic imaging modalities, the pathophysiology of dyspepsia is becoming better understood and recognized as an end point of multifactorial dysfunction of the enteric neural circuitry. Mechanism-targeted drugs, stem cell transplantation and electrical stimulation options are becoming available.

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This preliminary report suggests that there is an association between CRC and prostate cancer. If replicated in other populations, this may have important implications for cancer screening strategies.