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

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. AbstractThe 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.

A practical update on the epidemiology and risk factors for the emergence and mortality of bloodstream infections from real-world data of 3014 hematological malignancy patients receiving chemotherapy

“…Infection is the most common complication for patients with HM treated with chemotherapy 19 , 27 , and is a predictor for adverse outcomes. The most severe infections in these patients are BSIs, probably because of bone marrow suppression, neutropenia 28 and mucosal injury induced by chemotherapy 29 . The frequency of BSIs was 24.1% in this study, which is much higher than our previously reported for pre-engraftment patients in Ren et al (18.3%) 30 or reported for neutropenic patients in Wisplinghoff et al (14.3%) 7 .…”

The Utility of Grimace Scales for Practical Pain Assessment in Laboratory Animals

“…The majority of this validation work has occurred in rodent models. It is beyond the scope of this review to describe all of the models used but the range includes oncology (see e.g., [ 47 , 48 , 49 , 50 ]), infectious disease [ 51 ], pain models [ 48 , 52 , 53 ], neurological conditions [ 33 , 54 , 55 ], genetic conditions [ 56 ], and maxillofacial interventions [ 49 , 50 , 57 ]. However, the vast majority of research to date has performed grimace scoring retrospectively from captured video footage.…”

“…However, there was some investigation of a range of technologies which minimize the time taken for various aspects of this process. At the simplest level use of freeware video to JPG converter software can reduce the time associated with manual searching and capture of images from recorded video footage by automating the capture process [ 48 ]. However, this still requires manual viewing of the selected images to obtain unobstructed head shots.…”

The Utility of Grimace Scales for Practical Pain Assessment in Laboratory Animals

“…It is beyond the scope of this review to describe all of the models used but the range includes oncology (see e.g. [47][48][49][50] ), infectious disease 51 , pain models 48,52,53 , neurological conditions 33,54,55 , genetic conditions 56 , and maxillofacial interventions 49,50,57 . However, the vast majority of research to date has performed grimace scoring retrospectively from captured video footage.…”

“…However, there has been investigation of a range of technologies which minimize the time taken for various aspects of this process. At the simplest level use of freeware video to JPG converter software can reduce the time associated with manual searching and capture of images from recorded video footage by automating the capture process 48 . However, this still requires manual viewing of the selected images to obtain unobstructed head shots.…”