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Type: Journal article
Title: Differential effectiveness of clinically-relevant analgesics in a rat model of chemotherapy-induced mucositis
Author: Whittaker, A.
Lymn, K.
Wallace, G.
Howarth, G.
Citation: PLoS One, 2016; 11(7):e0158851-1-e0158851-19
Publisher: Public Library of Science
Issue Date: 2016
ISSN: 1932-6203
Statement of
Alexandra L. Whittaker, Kerry A. Lymn, Georgia L. Wallace, Gordon S. Howarth
Abstract: Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.
Keywords: Intestinal Mucosa; Animals; Rats; Disease Models, Animal; Peroxidase; Analgesics; Antineoplastic Agents; Behavior, Animal; Female; Mucositis
Rights: © 2016 Whittaker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030051397
DOI: 10.1371/journal.pone.0158851
Appears in Collections:Animal and Veterinary Sciences publications

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