Abstract
Background/Aims:Study of acute pancreatitis in chemically-induced rodent models has provided useful data; models of alcoholic chronic pancreatitis have not been available in mice. The aim of the present study was to characterize a mouse model of chronic pancreatitis induced solely with an alcohol and high fat (AHF) diet.Methods:Mice were fed a liquid high fat diet containing 6% alcohol as well as a high fat supplement (57% total dietary fat) over a period of five months or as control, normal chow ad libitum. Pain related measures utilized as an index of pain included mechanical sensitivity of the hind paws determined using von Frey filaments and a smooth/rough textured plate. A modified hotplate test contributed information about higher order behavioral responses to visceral hypersensitivity. Mice underwent mechanical and thermal testing both with and without pharmacological treatment with a peripherally restricted μ-opioid receptor agonist, loperamide.Results:Mice on the AHF diet exhibited mechanical and heat hypersensitivity as well as fibrotic histology indicative of chronic pancreatitis. Low dose, peripherally restricted opiate loperamide attenuated both mechanical and heat hypersensitivity.Conclusion:Mice fed an alcohol and high fat diet develop histology consistent with chronic pancreatitis as well as opioid sensitive mechanical and heat hypersensitivity.
Highlights
In 2004, pancreatitis in the US cost an estimated $373.3 million in direct and indirect costs [1]
Increased area of Sirius red stained fibrosis was identified in pancreas tissue samples from AHF fed mice compared to controls (Fig. 1F)
The present study demonstrated a non-invasive, alcohol and high fat diet induced mouse model of chronic pancreatitis that was produced in wildtype mice in the absence of noxious chemicals
Summary
In 2004, pancreatitis in the US cost an estimated $373.3 million in direct and indirect costs [1]. Eight in 100,000 people are diagnosed with chronic pancreatitis in the US yearly [2] and up to 50% of these individuals can live 20 years after diagnosis [3]. Fifty out of 100,000 people are living with chronic pancreatitis [4, 5]. Many of these patients endure severe intractable pain. The development of chronic pancreatitis in humans can result from multiple possible contributing risk factors, one of which is the sensitizing effect of alcohol on the pancreatic cells [6]. Alcohol-activated local pancreatic reactive immune cells, the stellate cells, and their interaction with other pancreatic and invading immune cell types contribute to
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