Su1971 The Effects of Oxytocin on Gastric Motility are Mediated by Different Neuronal Pathways in an Iodoacetamide Model of Functional Dyspepsia

Background: Insula represents an important site in the brain for multi-modal convergence and has been implicated in processing of visceral sensation. Earlier fMRI studies in humans (Lawall, et al. Am J Physiol 2008;294:G787-94) have shown activation and sensitization of insula in response to esophageal acid stimulation. However, response characteristics of insular neurons to esophageal chemical and mechanical stimulation have not been studied. Aims: Our aims in this study were: (i) to determine the influence of esophageal acid stimulation on the insular cortex neurons (ICNs) and (ii) to characterize the responses of these neurons to esophageal distension (ED) and colorectal distension (CRD) before and after esophageal acid exposure. Methods: Eleven male rats (SD, 300-400g) were initially anaesthetized with a mixture of α-chloralose (80mg/kg, i.p.) + urethane (800mg/kg, i.p.). The anesthetics were periodically supplemented (i.v.) every 3 hours with one-fourth of the initial dose and the blood pressure was constantly monitored. A craniotomy (Bregma: +2.5 to -2.5 mm, 2.0 to 7.0 mm lateral) was performed to access insular cortex (IC). Extracellular recordings from the ICNs (Bregma: +1.8 to -2.2 mm, 5.0 to 7.4 mm lateral, 5.8 to 7.8 mm dorso-ventral) were made from the neurons that responded to ED (30-60 mmHg) and/or CRD (30-60 mmHg). After characterization of ICNs to visceral stimulation (ED and CRD), 0.1 ml of PBS (0.1M, pH 7.4) was infused slowly (0.1ml/min) into the esophagus followed by the same volume of 0.1N HCl (pH 1.2). The infusate (0.1 ml) was applied three times at 60s, 300s and 540s. The interval of each infusion time was 4 minutes. The ED and CRD were repeated 15 minutes after acid infusion to study the responses of neurons. Results: Fifteen ED or CRD sensitive neurons were studied for their responses to PBS and acid infusion. All neurons (15/15, 100%) exhibited excitation (p<0.05) following acid infusion, whereas PBS had no effect on the responses of these neurons. Eleven EDand 10 CRDresponsive neurons were fully characterized to preand post-acid condition. Following acid infusion, 11/11 (100%) ED-responsive neurons exhibited increased activity in response to ED. In contrast, 10/10 (100%) CRD-responsive neurons exhibited decreased activity during CRD. In addition, acid, but not PBS, infusion increased the spontaneous firing of all recorded neurons and continued for 30 to 45 minutes after cessation of infusion. Conclusions: Intraesophageal acid infusion significantly alters the response characteristics of ICNs in rats. Esophageal acid infusion differentially modulates the activities of ICNs that receive convergent input from esophagus and colon.