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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Aug 6, 2016; 7(3): 370-386
Published online Aug 6, 2016. doi: 10.4292/wjgpt.v7.i3.370
Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes
Paul M Hobbs, William G Johnson, David Y Graham
Paul M Hobbs, William G Johnson, David Y Graham, Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX 77030, United States
Author contributions: Each of the authors have been involved equally in study design, data acquisition, analysis, interpretation and drafting the article; all have read and approved the final manuscript; each meets the criteria for authorship established by the International Committee of Medical Journal Editors and verify the validity of the results reported.
Conflict-of-interest statement: Dr. Graham is a paid consultant and has received research funding from RedHill Biopharma regarding novel H. pylori therapies and is a consultant to BioGaia regarding use of probiotics for H. pylori infections. He has nothing to declare in relation to this topic. Dr. Hobbs and Johnson also have nothing to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: David Y Graham, MD, Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, RM 3A-318B (111D), 2002 Holcombe Boulevard, Houston, TX 77030, United States. dgraham@bcm.edu
Telephone: +1-713-7950232 Fax: +1-713-7954471
Received: March 25, 2016
Peer-review started: March 25, 2016
First decision: May 17, 2016
Revised: June 8, 2016
Accepted: July 14, 2016
Article in press: July 18, 2016
Published online: August 6, 2016
Abstract

One of the most challenging issues arising in patients with chronic pancreatitis is the management of abdominal pain. Many competing theories exist to explain pancreatic pain including ductal hypertension from strictures and stones, increased interstitial pressure from glandular fibrosis, pancreatic neuritis, and ischemia. This clinical problem is superimposed on a background of reduced enzyme secretion and altered feedback mechanisms. Throughout history, investigators have used these theories to devise methods to combat chronic pancreatic pain including: Lifestyle measures, antioxidants, analgesics, administration of exogenous pancreatic enzymes, endoscopic drainage procedures, and surgical drainage and resection procedures. While the value of each modality has been debated over the years, pancreatic enzyme therapy remains a viable option. Enzyme therapy restores active enzymes to the small bowel and targets the altered feedback mechanism that lead to increased pancreatic ductal and tissue pressures, ischemia, and pain. Here, we review the mechanisms and treatments for chronic pancreatic pain with a specific focus on pancreatic enzyme replacement therapy. We also discuss different approaches to overcoming a lack of clinical response update ideas for studies needed to improve the clinical use of pancreatic enzymes to ameliorate pancreatic pain.

Keywords: Pancreatic enzyme replacement therapy, Chronic pancreatitis, Pancreatic insufficiency, Protease, Clinical trials, Trypsin, Fat malabsorption, Pain

Core tip: Pancreatic enzyme replacement therapy has long been used as a non-invasive treatment for chronic pancreatic pain. Enzyme therapy aims to restore feedback inhibition of pancreatic secretion to lessen pain caused by pancreatic ductal hypertension, increased pancreatic interstitial pressure, and pancreatic ischemia. Although enzyme therapy may play a role the key is individualization of therapy based on disease etiology and severity. Here we review the literature regarding the efficacy of enzyme therapy and the evidence gathered for an entero-pancreatic feedback loop. We also describe alternative strategies for improving pain therapy including using uncoated enzymes with gastric acid suppression.