Use of the Rat Grimace Scale to Evaluate Visceral Pain in a Model of Chemotherapy-Induced Mucositis.

Rebecca P George,Alexandra L Whittaker,Gordon S Howarth

doi:10.3390/ani9090678

Abstract

Simple SummaryMucositis is a painful and often debilitating condition associated with cancer treatment. Management of associated symptoms is an important clinical consideration. Animal models are used in mucositis research to model the condition in humans in order to develop novel therapeutic agents to relieve symptoms. Previous animal studies have focused on disease severity and outcomes, but often failed to measure pain. The rat grimace scale (RGS) is a validated observational measure used to gauge pain levels experienced by rats. The aim of this study was to assess the rat grimace scale in a rat model of mucositis, and to examine whether changes in clinical signs and anxiety reflected the grimace responses recorded. We also aimed to determine whether the responses were pain-specific by administering potent opioid painkilling agents. In the present study rat grimace scores did not change significantly between treatments. Development of reliable pain assessment methods in animal models is urgently required to improve model relevance to human clinical practice, in addition to safeguarding animal welfare. The rat grimace scale (RGS) is a measure of spontaneous pain that evaluates pain response. The ability to characterize pain through a non-invasive method has considerable utility for numerous animal models of disease, including mucositis, a painful, self-limiting side-effect of chemotherapy treatment. Preclinical studies investigating novel therapeutics for mucositis often focus on pathological outcomes and disease severity. These investigations fail to measure pain, in spite of reduction of pain being a key clinical therapeutic goal. This study assessed the utility of the RGS for pain assessment in a rat model of mucositis, and whether changes in disease activity index (DAI) and open field test (OFT) reflected the grimace responses recorded. Sixty tumor-bearing female Dark Agouti rats were injected with either saline or 5-Fluourouracil alone, or with co-administration of opioid analgesics. Whilst differences in DAI were observed between treatment groups, no difference in RGS scores or OFT were demonstrated. Significant increases in grimace scores were observed across time. However, whilst a statistically significant change may have been noted, the biological relevance is questionable in terms of practical usage, since an observer is only able to score whole numbers. Development of effective pain assessment methods in animal models is required to improve welfare, satisfy regulatory requirements, and increase translational validity of the model to human patients.

Highlights

Mucositis is a painful and debilitating condition arising in 40–60% of oncology patients treated with chemotherapeutic agents [1]
The aim of the current study was to assess the utility of the rat grimace scale (RGS) for pain assessment in female Dark Agouti tumor-bearing rats with chemotherapy-induced mucositis
‘pain face’, and secondly, experiencing mucositis displayed pain as determined through expression of a ‘pain face’, and whether this pain could be ameliorated through the use of potent analgesics, validating secondly, whether this pain could be ameliorated through the useopioid of potent opioid analgesics, the as a pain measure in this model

Summary

Introduction

Mucositis is a painful and debilitating condition arising in 40–60% of oncology patients treated with chemotherapeutic agents [1]. Pain may arise directly due to the activation of nociceptors [3], or in response to other gastrointestinal events such as abdominal bloating and ulceration [4]. A range of research programs are directed at further elucidating the mechanisms of mucositis pathogenesis, and development of novel therapeutic agents for symptomatic relief of symptoms [5,6]. Many of these programs of research utilize animal models

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