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.
Highlights
Chemotherapy represents the first-line approach for cancer treatment, yet side-effects remain significant
Analgesics in a Rat Model of Chemotherapy-Induced Mucositis more commonly associated with mucositis development; the chemotherapy drug 5-fluorouracil is one such agent [2]
This study represents the first published investigation into analgesics administered to rats with experimentally-induced mucositis
Summary
Chemotherapy represents the first-line approach for cancer treatment, yet side-effects remain significant. One such side-effect is mucositis, which results from a series of biological events initiated by the epithelial cell response to cytotoxic damage [1]. Analgesics in a Rat Model of Chemotherapy-Induced Mucositis more commonly associated with mucositis development; the chemotherapy drug 5-fluorouracil is one such agent [2]. Mucositis affects all mucous-membrane covered surfaces from the mouth to the rectum, and remains the main dose limiting factor in cancer treatment [3, 4]. Mucositis is thought to be the resultant effect of a range of cytokine-mediated events culminating in mucosal atrophy and ulceration [5]. Epithelial sloughing, mucosal inflammation and ulceration activate nociceptors causing a direct pain response [6]. Patients typically require potent opioid analgesics for pain control during extended periods of hospitalisation [6]
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