Performance of behavioral assays: the Rat Grimace Scale, burrowing activity and a composite behavior score to identify visceral pain in an acute and chronic colitis model

Leung, Vivian Sy; Benoit‐Biancamano, Marie‐Odile; Pang, Daniel S. J.

doi:10.1097/pr9.0000000000000712

Cited by 26 publications

(25 citation statements)

References 35 publications

(54 reference statements)

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“…Subsequently, others have reported that chronic pain may be identified using grimace scales in other models, notably colitis (dextran sodium sulphate-induced), cervical radiculopathy (surgical compression model), neuralgia (chronic constriction injury of the infraorbital nerve), orofacial pain (movement or load-induced), spinal cord injury (cord impact model) and migraine (nitroglycerin-induced) in rats and mice. 2,6,48,74,80,112,134,152 These data suggest that limiting application of the MGS and RGS to acute pain may be premature.…”

Section: Physiologic Assessments Of Pain In Laboratory Mice and Ratsmentioning

confidence: 99%

“…29 In rats, scoring of burrowing behavior has been employed successfully in Hooded Lister, Wistar and Sprague-Dawley strains. 3,29,52,69 Burrowing is reduced in a wide range of pain models in rats and mice, including laparotomy, 4,58-60 colitis and mucositis, 57,74,144 neuropathic pain, 3,52,69,95,124 inflammation, 3,46,95,130,139,144,147 and arthritis. 12,125,126 In addition, many of these studies have confirmed responsiveness, showing either an improvement or return to baseline burrowing behavior following the administration of antiinflammatories and analgesics.…”

Section: Burrowing Behaviorsmentioning

confidence: 99%

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A Review of Pain Assessment Methods in Laboratory Rodents

2019

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Ensuring that laboratory rodent pain is well managed underpins the ethical acceptability of working with these animals in research. Appropriate treatment of pain in laboratory rodents requires accurate assessments of the presence or absence of pain to the extent possible. This can be challenging some situations because laboratory rodents are prey species that may show subtle signs of pain. Although a number of standard algesiometry assays have been used to assess evoked pain responses in rodents for many decades, these methods likely represent an oversimplification of pain assessment and many require animal handling during testing, which can result in stress-induced analgesia. More recent pain assessment methods, such as the use of ethograms, facial grimace scoring, burrowing, and nest-building, focus on evaluating changes in spontaneous behaviors or activities of rodents in their home environments. Many of these assessment methods are time-consuming to conduct. While many of these newer tests show promise for providing a more accurate assessment of pain, most require more study to determine their reliability and sensitivity across a broad range of experimental conditions, as well as between species and strains of animals. Regular observation of laboratory rodents before and after painful procedures with consistent use of 2 or more assessment methods is likely to improve pain detection and lead to improved treatment and care—a primary goal for improving overall animal welfare.

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Section: Physiologic Assessments Of Pain In Laboratory Mice and Ratsmentioning

confidence: 99%

Section: Burrowing Behaviorsmentioning

confidence: 99%

A Review of Pain Assessment Methods in Laboratory Rodents

2019

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“…However, previous studies involved a surgical stimulus [28,29,30], or inflammatory pain model [28], hence pain duration in the current study may have been reduced in comparison to the visceral pain sensation of mucositis. Contrarily, an assumed chronic pain insult caused by tooth movement caused a grimace response in rats for several days post-pain insult [31], as did the presence of colitis [14]. It is noteworthy that in the current study, grimace values were a small fraction of the maximum obtainable score (i.e., 8); often scoring under one.…”

Section: Discussionmentioning

confidence: 72%

“…The disease activity index (DAI) evaluates disease severity based on general clinical observations; overall appearance of the animals, bodyweight loss, rectal bleeding and stool consistency. While an association between clinical signs and pain has been demonstrated in gastrointestinal disorders in human clinical practice, this has not been validated in rodent models of mucositis [3,14]. The open field test is a well validated measure of anxiety in rodent models.…”

Section: Introductionmentioning

confidence: 99%

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

George

Howarth

Whittaker

2019

Animals

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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.

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“…It is important to note that the original derivation of the threshold was in adult PLOS ONE female SD rats that underwent surgery involving the skin and muscular systems. However, recent work showed that the RGS and intervention threshold identified the onset of acute and chronic colitis (a model of visceral pain) in male and female SD rats [20,35]. The RGS and intervention threshold has also been successfully applied to distinguish analgesic effects in female Wistar rats (laparotomy model, analgesic testing) [36,37].…”

Section: Limitations and Future Studiesmentioning

confidence: 99%

Intraperitoneal injection of sodium pentobarbital has the potential to elicit pain in adult rats (Rattus norvegicus)

et al. 2020

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An effective and pain-free killing method is required to achieve the goal of euthanasia, a "good death". Overdose of sodium pentobarbital (PB) by intraperitoneal (IP) injection is a widely accepted technique in laboratory rats, but questions remain regarding pain associated with administration. As PB rapidly causes sedation and loss of consciousness, most studies have relied on indirect evidence of pain. The objective of this study was to assess pain associated with IP PB using an appropriate vehicle control. Adult male and female Sprague Dawley (SD) and female Wistar rats (N = 84) were block randomised by sex and strain to receive one of three treatments: 1) 800 mg/kg PB (pH 11), 2) saline or 3) vehicle controls (pH 11 or 12.5). Behavior (Rat Grimace Scale (RGS), writhing, back arching) was evaluated at baseline, before loss of righting reflex (LORR, PB group), and at 80s, 151s and 10 min post-injection (PI; saline and vehicle control groups). In the PB group, mean time to LORR was 78 ± 7.9 seconds. In the vehicle control groups, RGS scores were increased at 151s PI (SD: p = 0.0002, 95%CI 0.73 to 0.20) from baseline, as was relative frequency of writhing (SD: p < 0.0001; Wistar; p = 0.0004). RGS scores remained elevated 10 mins PI (SD: p = 0.0005, 95%CI 0.71 to 0.18; Wistar: p = 0.0234, 95%CI 0.91 to 0.07) but the relative frequency of writhing did not (p > 0.999). The RGS scores and the relative frequency of writhing remained low in the PB and saline groups (p > 0.05). These results show that, vehicle controls for IP PB result in signs associated with pain, pain may not be experienced following IP PB when LORR occurs quickly, and that the effects of PB limit behavioral pain assessments.

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Performance of behavioral assays: the Rat Grimace Scale, burrowing activity and a composite behavior score to identify visceral pain in an acute and chronic colitis model

Abstract: Supplemental Digital Content is Available in the Text. The ability of spontaneous behavioral assays to assess chronic pain is limited. In colitis, RGS identified acute and chronic pain, burrowing identified acute pain.

Cited by 26 publications

References 35 publications

A Review of Pain Assessment Methods in Laboratory Rodents

A Review of Pain Assessment Methods in Laboratory Rodents

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

Intraperitoneal injection of sodium pentobarbital has the potential to elicit pain in adult rats (Rattus norvegicus)

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