Beneficial Effects of Ropivacaine in Rat Experimental Colitis1

Ropivacaine, a new, long-acting local anesthetic agent, has been shown to have beneficial effects in the treatment of ulcerative colitis. Treatment with this drug results in prompt symptomatic relief. The aim of this study was to examine the effects of ropivacaine on mucosal healing and to investigate whether ropivacaine can restore the decreased colonic contractility seen in the diseased state. Colitis was induced in rats by a single intrarectal administration of trinitrobenzene sulfonic acid. Mucosal healing was assessed after 1 week of therapy. The effects on colonic contractility were examined either after 1 week of treatment or by application of the drugs to untreated, inflamed rat colon segments placed in organ baths. After the induction of colitis, daily intracolonic treatment with ropivacaine for 1 week reduced morphological damage and myeloperoxidase activity. One week of treatment also restored the contractile response to acetylcholine. By adding ropivacaine directly to untreated inflamed colonic segments in organ baths, the contractile response to acetylcholine was increased compared with controls. For comparison, the effects of budesonide and 5-aminosalicylic acid were also examined. Ropivacaine improved mucosal healing and restored colonic motor activity in experimental colitis, similar to budesonide but superior to 5-aminosalicylic acid. Ropivacaine, a new local anesthetic agent currently under investigation for the treatment of ulcerative colitis (UC), improves inflammatory endoscopic scores after only 2 weeks of treatment (Arlander et al., 1996). In experimental studies, ropivacaine has been found to inhibit leukocyte adhesion and expression of adhesion molecules (Martinsson et al., 1997b) and the formation of leukotriene B4 (LTB4), and reactive oxygen metabolites (Cederholm et al., 1994; Martinsson et al., 1997a) from human neutrophils. These observations are in line with several previous studies indicating anti-inflammatory effects of local anesthetic agents other than ropivacaine (Cullen and Haschke, 1974; MacGregor et al., 1980; Sinclair et al., 1993). Inflammation of the gastrointestinal tract results in the disturbance of motility in humans and in animal models. The disruption of normal motor patterns in intestinal inflammation, including colonic hypomotility and unresponsiveness to contractile stimuli, contributes to commonly observed clinical features, such as diarrhea (Spriggs et al., 1951; Snape et al., 1980; Wallace et al., 1991). The changes in colonic motility and secretion may reflect alterations in the function of smooth muscle or the enteric nervous system, or both. Restoration of colonic motility may perhaps explain the observation that daily intrarectal administration of local anesthetic agents commonly results in symptomatic relief (within a few days) in patients with UC (Björck et al., 1993). The aim of this study was to investigate the contractile responses in vitro of normal and inflamed rat colon and to investigate the effects of ropivacaine on contractions of colonic smooth muscle induced by acetylcholine (ACh). Furthermore, we examined the ability of ropivacaine to modify the course of mucosal pathology in experimental colitis induced in the rat with trinitrobenzene sulfonic acid (TNBS). Materials and Methods