The Open Pain Journal

2017, 10 : 81-89
Published online 2017 September 15. DOI: 10.2174/1876386301710010081
Publisher ID: TOPAINJ-10-81

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 and K.N. Westlund2, *

* 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.