RESEARCH ARTICLE


A Mouse Model of Chronic Pancreatitis Induced by an Alcohol and High Fat Diet



T. Clinkinbeard1, 2, R.H. Kline2, L.P. Zhang2, S.L. McIlwrath2, J.F. Watkins1, K.N. Westlund2, *
1 Center for Gerontology, School of Public Health, University of Kentucky, 725 Rose St., Lexington, KY 40536, USA
2 Department of Physiology, School of Medicine, University of Kentucky, 800 Rose St., Lexington, KY 40536-0298, USA


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© 2017 Clinkinbeard et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondance to this author at the Department of Physiology, School of Medicine, University of Kentucky, 800 Rose St., Lexington, KY 40536-0298, USA; Tel: 505 272-7417; E-mail: khigh@salud.unm.edu


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.

Keywords: Loperamide, Mu opioid, Hypersensitivity, Pain, Nociception, Pancreas, Fibrosis, Behavioral test.