Effects and underlying mechanisms of endotoxemia on post-incisional pain in rats

Kawano, Takashi; Eguchi, Satoru; Iwata, Hisato; Yamanaka, Daiki; Tateiwa, Hiroki; Locatelli, Fabricio M.; Yokoyama, Masataka

doi:10.1016/j.lfs.2016.01.046

Cited by 16 publications

(13 citation statements)

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“…Low doses of these NSAIDs have been repeatedly reported to reduce CBS behaviours; however, these same NSAIDs were reported as either ineffective at reducing RGS scores or a https://doi.org/10.1371/journal.pone.0209467.g002 much higher dose was required [8-10, 13, 20, 21]. For example, ketoprofen at 5 mg/kg significantly reduced the frequency of CBS behaviours but a higher dose of 25-40 mg/kg was required to reduce RGS scores significantly, a dose range associated with adverse gastrointestinal effects [8,13,[20][21][22][23]. At high doses, ketoprofen is as effective as 0.8 mg/kg of morphine in reducing RGS scores [21].…”

Section: Discussionmentioning

confidence: 99%

Comparing the Rat Grimace Scale and a composite behaviour score in rats

Klune

Larkin²,

Leung

et al. 2019

PLoS ONE

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There is a growing interest in the use of voluntarily displayed ongoing behaviours in laboratory animals to assess the pain experience. In rats, two behavioural pain scales, the Rat Grimace Scale (RGS, a facial expression scale) and a composite behaviour score (CBS, a behavioural ethogram reliant on postural changes), are both promising pain assessment methods. Both scales have been used to assess pain in a laparotomy model, however, they have never been compared directly and the knowledge of how different analgesics may affect these two scales is limited. This study aimed to provide a comparison to discriminate the temporal and analgesic response in a laparotomy model. Female Wistar (n = 26) and Sprague Dawley rats (n = 26) were block randomized to receive saline, meloxicam (2 mg/ kg) or buprenorphine (0.05 mg/kg) 30 minutes before laparotomy. Rats were video-recorded before surgery (BL) and at 30, 150, 270, and 390 minutes post-operatively. Videos were assessed according to both scales by a trained, blinded observer. Both CBS and RGS scores increased significantly at all post surgical timepoints in the saline group. Both buprenorphine and meloxicam reduced CBS scores to baseline levels following laparotomy; however, RGS scores were only reduced following buprenorphine. RGS scores in the meloxicam group remained similar to scores of the saline group. These findings suggest that the CBS and RGS differ in their sensitivity to discriminating analgesic effects.

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Section: Discussionmentioning

confidence: 99%

Comparing the Rat Grimace Scale and a composite behaviour score in rats

Klune

Larkin²,

Leung

et al. 2019

PLoS ONE

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“…Similar observations have also been reported with two other types of NSAIDs: ketoprofen and carprofen. Low doses of these NSAIDs have been repeatedly reported to reduce CBS behaviours, however, these same NSAIDs were reported as either ineffective at reducing RGS scores or a much higher dose was required [8-10, 13, 19, 20]. For example, ketoprofen at 5 mg/kg significantly reduced the frequency of CBS behaviours but a higher dose of 25-40 mg/kg was required to reduce RGS scores significantly [8, 13, 19, 20].…”

Section: Discussionmentioning

confidence: 99%

“…Low doses of these NSAIDs have been repeatedly reported to reduce CBS behaviours, however, these same NSAIDs were reported as either ineffective at reducing RGS scores or a much higher dose was required [8-10, 13, 19, 20]. For example, ketoprofen at 5 mg/kg significantly reduced the frequency of CBS behaviours but a higher dose of 25-40 mg/kg was required to reduce RGS scores significantly [8, 13, 19, 20]. At high doses, it was reported that ketoprofen was as effective as 0.8 mg/kg of morphine at reducing RGS scores [20], however, it has also been reported that gastrointestinal side effects occur at doses as low as 5 mg/kg [13, 21, 22].…”

Section: Discussionmentioning

confidence: 99%

Comparing the Rat Grimace Scale and a composite behaviour score in rats

Klune

Larkin

Leung

et al. 2018

Preprint

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22There is a growing interest in the use of voluntarily displayed ongoing behaviours in laboratory 23 animals to assess the pain experience. In rats, two behavioural pain scales, the Rat Grimace Scale 24 (RGS, a facial expression scale) and a composite behaviour score (CBS, a behavioural ethogram 25 reliant on postural changes), are both promising pain assessment methods. Both scales have been 26 used to assess pain in a laparotomy model, however, they have never been compared directly and 27 the knowledge of how different analgesics may affect these two scales is limited. This study 28 aimed to provide a comparison to discriminate the temporal and analgesic response in a 29 laparotomy model. Female Wistar (n = 26) and Sprague Dawley rats (n = 26) were block 30 randomized to receive saline, meloxicam (2 mg/kg) or buprenorphine (0.05 mg/kg) 30 minutes 31 before a laparotomy model. Rats were video-recorded before surgery (BL) and at 30, 150, 270, 32 and 390 minutes post-operatively. Videos were assessed according to both scales by a trained, 33 blinded observer. Both CBS and RGS scores increased significantly at all post surgical 34 timepoints in the saline group. Post-surgical CBS scores did not increase significantly above 35 baseline levels in the groups given meloxicam or buprenorphine. However, the RGS scores only 36 remained low in the buprenorphine group while scores increased significantly in the meloxicam 37 group, to a similar degree as in the saline group. These findings suggest that the CBS is more 38 sensitive to the analgesic effects of NSAIDs than the RGS. 39 Introduction 40Accurate and reliable pain assessment in laboratory rodents is essential to produce high 41 quality pain research and safeguard animal welfare. The continued dependence on evoked 42 hypersensitivity to assess pain in animals has been proposed as a contributor towards failure of 43 translational research. While measures of evoked hypersensitivity assess hyperalgesia and 44 allodynia, they do not capture ongoing pain which has been suggested to be most relevant in 45 many human pain conditions [1][2][3][4][5]. Ongoing pain is perpetuated by an ongoing inflammatory 46 process rather than an external stimulus. Multiple methods have been proposed to evaluate 47 ongoing pain in animals, however, a lack of evidence describing the strengths and weaknesses of 48 such methods in comparison to one another discourages their use [3]. 49From a welfare perspective, signs associated with pain are common humane endpoints in 50 rodent research, but typical signs such as weight loss may not be specific to pain or sufficiently 51 sensitive to be useful [6]. Traditional nociceptive tests, such as mechanical withdrawal testing, 52 are not used as welfare assessment tools as they are time consuming and labour intensive. 53 Two promising behavioural assessment methods have been developed to better capture 54 the ongoing pain experience of laboratory rodents. These are the Rat Grimace Scale (RGS) [7] 55 and the short form Composite Behaviour Sc...

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“…The test should demonstrate an absence of pain before the painful stimulus, an increase in pain at the introduction of the painful stimulus, and a subsequent reduction in observed pain on the delivery of an appropriate analgesic [ 7 , 36 ]. Ideally, the test should be able to demonstrate a dose–responsive curve to pain based on the administration of appropriate analgesia [ 40 , 41 , 42 , 43 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

“…The FAUs related to the expression of a grimace face in mammalian animals used in research are included in Table 4 . From this known ‘grimace face’, the severity of the pain experienced can be objectively scored from images and/or film of animals in a known naturally (i.e., lameness, mastitis) [ 37 , 82 , 85 ] or experimentally induced (i.e., plantar incision [ 41 , 44 , 103 ] state of pain.…”

Section: Introductionmentioning

confidence: 99%

Grimace Scores: Tools to Support the Identification of Pain in Mammals Used in Research

Cohen

Beths

2020

Animals

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The 3Rs, Replacement, Reduction and Refinement, is a framework to ensure the ethical and justified use of animals in research. The implementation of refinements is required to alleviate and minimise the pain and suffering of animals in research. Public acceptability of animal use in research is contingent on satisfying ethical and legal obligations to provide pain relief along with humane endpoints. To fulfil this obligation, staff, researchers, veterinarians, and technicians must rapidly, accurately, efficiently and consistently identify, assess and act on signs of pain. This ability is paramount to uphold animal welfare, prevent undue suffering and mitigate possible negative impacts on research. Identification of pain may be based on indicators such as physiological, behavioural, or physical ones. Each has been used to develop different pain scoring systems with potential benefits and limitations in identifying and assessing pain. Grimace scores are a promising adjunctive behavioural technique in some mammalian species to identify and assess pain in research animals. The use of this method can be beneficial to animal welfare and research outcomes by identifying animals that may require alleviation of pain or humane intervention. This paper highlights the benefits, caveats, and potential applications of grimace scales.

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Effects and underlying mechanisms of endotoxemia on post-incisional pain in rats

Cited by 16 publications

References 30 publications

Comparing the Rat Grimace Scale and a composite behaviour score in rats

Comparing the Rat Grimace Scale and a composite behaviour score in rats

Comparing the Rat Grimace Scale and a composite behaviour score in rats

Grimace Scores: Tools to Support the Identification of Pain in Mammals Used in Research

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