Su2000 Reduced Small Bowel Transit is Associated With Enhanced Excitability of Sympathetic Prevertebral Ganglion Neurons but Not Ileum Myenteric Neurons During Colitis in Guinea Pigs

Abstract

Background: Localized colitis causes a reduction in small bowel motor function in humans and non-human animals yet the mechanisms that contribute to this phenomenon is not completely understood. Aim: To determine the time course of changes in 1) small bowel motor function, 2) excitability of ileum myenteric plexus neurons and 3) excitability of inferior mesenteric ganglion (IMG) neurons following an inflammatory insult to the distal colon. Methods: Colitis was induced by a single enema of trinitrobenzene sulfonic acid (TNBS) dissolved in 30% EtOH. Small bowel transit was assessed by determining the location of the leading edge of charcoal 30min following gavage and reported as a percentage of the total length of the small intestine. Neuronal excitability was assessed by conventional intracellular electrophysiology. Results: Small bowel transit was reduced in guinea pigs 12h, and 24h post-TNBS, but returned to normal at 48h and 6d post-TNBS (control, 84±3;12h, 50±9; 24h, 44±3; 48h, 68±8; 6d, 75±2;P<0.05). AH neurons of the guinea pig ileum were hyperexcitable at 24h 48h and 6d post-TNBS, but were not different than controls at 12h post-TNBS. Evidences of excitability were a more depolarized membrane potential (mV: control, -76±3;12h, -73±2; 24h, -59±2; 48h, -63±2; 6d, -68±3;P<0.05), and increased number of action potentials (control, 1.2±0.2;12h, 1.1±0.7; 24h, 3.5±1.2; 48h, 4.5±1.3; 6d, 7.8±3.0;P<0.05). There was no change in the magnitude of the afterhyperpolarization or the threshold current. Tonic neurons of the IMG were hyperexcitable at 12h, 24h and 6d post-TNBS, the three time points tested. Evidences of excitability were a decreased threshold current (pA: control, 340±26;12h, 258±23; 24h, 192±17; 6d, 164±18;P<0.05), and increased number of action potentials (control, 3.1±0.1;12h, 5.7±0.7; 24h, 6.2±0.4; 6d, 5.1±0.3;P<0.05). There was no change in resting membrane potential. Conclusion: Reduced small bowel transit 12h following TNBS suggests rapid functional changes in response to the inflammatory insult. There is no evidence for excitability of myenteric AH neurons at this early time point so these cells may not directly contribute to the functional change. Conversely, PVG neurons are excitable at this early time point. This association supports the concept that PVG neurons contribute to small bowel motor dysfunction during colitis. The mechanisms contributing the later excitability of myenteric AH neurons and restoration of normal transit despite ongoing neuronal hyperexcitability remain unresolved. Supported by NIH Grant DK76665.