Changes in colonic motility and the electrophysiological properties of myenteric neurons persist following recovery from trinitrobenzene sulfonic acid colitis in the guinea pig

Abstract

Persistent changes in gastrointestinal motility frequently accompany the resolution of colitis, through mechanisms that remain to be determined. Trinitrobenzene sulfonic acid (TNBS) colitis in the guinea pig decreases the rate of propulsive motility, causes hyperexcitability of AH neurons, and induces synaptic facilitation. The changes in motility and AH neurons are sensitive to cyclooxygenase-2 (COX-2) inhibition. The aim of this investigation was to determine if the motility and neurophysiological changes persist following recovery from colitis. Evaluations of inflammation, colonic motility and intracellular electrophysiology of myenteric neurons 8 weeks after TNBS administration were performed and compared to matched control conditions. Myeloperoxidase levels in the colons were comparable to control levels 56 days after TNBS treatment. At this time point, the rate of colonic motility was decreased relative to controls following treatment with TNBS alone or TNBS plus a COX-2 inhibitor. Furthermore, the electrical properties of AH neurons and fast synaptic potentials in S neurons were significantly different from controls and comparable to those detected during active inflammation. Collectively, these data suggest that altered myenteric neurophysiology initiated during active colitis persists long term, and provide a potential mechanism underlying altered gut function in individuals during remission from inflammatory bowel disease.

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

“…This colitis is transient, peaking several days after administration and then spontaneously healing such that by 28 days following administration the histology of the colon and myeloperoxidase levels do not differ from untreated animals (Hughes et al, 2009a;Hughes et al, 2009b;Krauter et al, 2007;Qin et al, 2011). However, colonic afferent nerves remain sensitized to distension long after the mucosa heals, which models aspects of the chronic visceral hypersensitivity (CVH) experienced by IBS patients (Gschossmann et al, 2004;Hughes et al, 2009a;Hughes et al, 2009b).…”

Spatiotemporal Mapping of Motility in <em>Ex Vivo</em> Preparations of the Intestines

“…Video recording and spatiotemporal mapping of intestinal and colonic segments have been applied to a variety of species including zebrafish 26 , mouse 25,[27][28][29][30] , rat 7,9,[30][31][32][33] , guinea pig 5,6,8,[13][14][15][16][17][18][19]24,30,32,34,35 , brushtail possum 12,36 , rabbit 2,30,37,38 , chicken 39 , pig 40,41 and human 42 . The most widely studied species is the guinea pig.…”

“…The construction of STmaps and analysis of changes in motility pattern have been applied to key questions in the gastrointestinal motility of intestine and colon. These include: differentiation of neurogenic and myogenic contractions and defining the role of interstitial cells of Cajal 6,9,11,12,16,24,26,27,[29][30][31]33,[37][38][39][40]42 , understanding the complex interactions between the circular and longitudinal muscle layers 2,7,8,11,12,32,39,40 , examining the effects of intraluminal nutrients 10,18,19 , microbial strains 34 , and viscosities 12,36 on various motility patterns, and understanding the role of various endogenous neurohormonal agents and exogenous pharmacological agents 2,[4][5][6][7]9,10,[13][14][15][16][17]28,35,40 in the generation and modification of motility...…”

“…While many groups have generated their own software packages or plugins, they all analyze diameters of a tissue segment and convert those various diameters to grayscale representation. A commercially available recording and analysis system called the GastroIntestinal Motility Monitoring system (GIMM) provides a turnkey approach that allows for analysis of both propulsive motility via fecal pellet velocity determination in the guinea pig distal colon 13 as well as analysis of propulsive and mixing motility patterns with a fluid stimulus in intact intestinal segments 4,5,[14][15][16][17][18][19] 4. General Experimental Procedures 1.…”

Fundamentals of Neurogastroenterology: Basic Science

“…Therefore, inflammation-induced changes in neuronal function could be a contributing factor in IBS and refractory inflammatory bowel disease, but these changes in neuronal excitability and synaptic strength would not be detectable with current diagnostic techniques. Several inflammation-induced changes in the ENS, including AH neuron hyperexcitability, do persist beyond recovery of inflammation, 25,26 supporting the possibility that long-term changes in enteric circuitry could contribute to FGIDs.…”