Animal models for investigating chronic pancreatitis

Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis, areas of focal necrosis are typically followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct and by the development of pseudocysts. Late in the course of the disease, a progressive loss of endocrine and exocrine function occurs [1-3].With an incidence of 8.2, a prevalence of 27.4 per 100 000 population and a frequency of presence in 0.04% to 5% of all autopsies performed, chronic pancreatitis represents a common disorder of the gastrointestinal tract [4-6]. The etiology of this disease is complex and so far a variety of environmental factors including alcohol use, smoking and exposure to other toxic agents as well as endogenous factors such as genetic variations have been described. Chronic pancreatic and biliary tract obstruction or congenital malformations also contribute to development of chronic pancreatitis. Despite advances in the diagnosis of chronic pancreatitis, available treatments are still unsatisfactory because therapeutic concepts are mostly restricted to relieving symptoms rather than changing the natural history [6,7].The pathogenesis of chronic pancreatitis is still poorly understood. Alcohol use is the leading risk factor and the most common etiology [8]. At present there are four competing hypotheses concerning the pathogenesis of chronic pancreatitis that are largely historic. According to Bordalo et al., ethanol induces a fatty degeneration of acinar tissue similar to that seen in hepatocytes during alcoholic liver disease. Ethanol has either a direct or an indirect toxic effect, mediated by the ethanol metabolite acetaldehyde, on the integrity of pancreatic acinar cells [8-10].Braganza et al. proposed a toxic effect of oxygen-de