Inflammation of the intestine causes pain and altered motility , at least in part through effects on the enteric nervous system. While these changes may be reversed with healing , permanent damage may contribute to inflammatory bowel disease (IBD) and post-enteritis irritable bowel syndrome. Since little information exists , we induced colitis in male Sprague-Dawley rats with dinitrobenzene sulfonic acid and used immunocytochemistry to examine the number and distribution of enteric neurons at times up to 35 days later. Inflammation caused significant neuronal loss in the inflamed region by 24 hours , with only 49% of neurons remaining by days 4 to 6 and thereafter , when inflammation had subsided. Eosinophils were found within the myenteric plexus at only at the earliest time points , despite a general infiltration of neutrophils into the muscle wall. While the number of myenteric ganglia remained constant , there was significant decrease in the number of ganglia in the submucosal plexus. Despite reduced neuronal number and hyperplasia of smooth muscle , the density of axons among the smooth muscle cells remained unchanged during and after inflammation. Intracolonic application of the topical steroid budesonide caused a dose-dependent prevention of neuronal loss , suggesting that evaluation of anti-inflammatory therapy in inflammatory bowel disease should include quantitative assessment of neural components. (Am J Pathol 1999, 155:1051-1057)Inflammatory bowel disease (IBD) is a chronic idiopathic inflammation of the intestine that affects an increasing percentage of the population in Western society, with the highest incidence among the younger population, for whom there are no specific or effective treatments. The broad acting anti-inflammatory agents in wide use have serious side effects of immune suppression, loss of bone calcium, and growth retardation. Therefore, a strong need exists for increased information about the cellular basis of this disease, as well as new pharmacological tools and improved methods of use.Studies of IBD have relied heavily on immunological approaches, relating activation of immune cells to the periodic exacerbation and remissions of disease. However, a particular challenge lies in understanding the long-term or permanent changes present in the intestine in IBD, which are evident even in the periods of remission between acute episodes. Recently, attention has been paid to the other cell types in the intestine that may acquire the ability to participate in inflammation or that are previously unexpected targets of inflammatory change.1 This has shown that nonimmune cells can participate directly in inflammation, as well as pointing out the potential for long-term alterations in cell structure and function that may predispose to repeated episodes of inflammation. Thus, intestinal smooth muscle has been shown to have the potential to present antigen to activated T cells and may also be a source of cytokines that can directly affect neural function. 1,2Most, if not all, aspects of normal...

Inflammation of the rat jejunum with Trichinella spiralis causes altered smooth muscle contractility by day 6 postinfection (PI). We investigated the association of structural change in the smooth muscle layers with inflammation. By day 6 PI, smooth muscle area in cross sections of jejunum increased (P less than 0.05) in longitudinal (LM) and circular (CM) muscle layers. Nuclei counting in cross sections showed that cell number increased two- to threefold in CM and LM, and this increase was not reversed on day 23 PI. Estimation of cell size showed significant hypertrophy by day 6 PI in both muscle layers. [3H]thymidine autoradiography showed that the labeling index (LI) of jejunal LM and CM increased sharply on day 4 PI and peaked on day 6 PI (10- to 15-fold increase). The noninflamed ileum showed a smaller trophic response, with no significant change in area or nuclei number, the LI was increased only on day 6 PI in the ileal CM and was unchanged in LM. Thus extensive hyperplasia and hypertrophy of smooth muscle cells are associated with intestinal inflammation.

We investigated the involvement of nitric oxide in trinitrobenzene-sulfonic acid (TNB) colitis. Every 24 h after TNB, rats were orally dosed with NG-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg), NG-nitro-D-arginine methyl ester (D-NAME), or water, and food intake, body weight, and plasma nitrite levels were measured. On day 6, colonic nitric oxide synthase and myeloperoxidase (MPO) activity, histology, intestinal muscle growth, NADPH-diaphorase, and myenteric nerve function were assessed. Food intake and body weight were reduced during the first 72 h of colitis. On day 6 post-TNB, a fourfold increase in mucosal nitric oxide synthase, a 30-fold increase in MPO, and a fivefold elevation in plasma nitrite were measured. Smooth muscle hyperplasia and hypertrophy in both colonic muscle layers, numerous diaphorase-positive macrophages in the myenteric plexus, and a suppression of myenteric nerve function were also observed. Unlike D-NAME, oral L-NAME reduced MPO and intestinal muscle hyperplasia by > 90%. Likewise, plasma nitrite and colonic nitric oxide synthase were reduced by > 70%. L-NAME completely prevented macrophage infiltration into the muscle. Conversely, it had no effect on anorexia or intestinal smooth muscle hypertrophy, nor did it affect suppressed myenteric nerve neurotransmitter release. These results demonstrate the selective transmural protective effects of L-NAME in the inflamed colon, implicating nitric oxide as a mediator.