A model-specific simplification of the Mouse Grimace Scale based on the pain response of intraperitoneal CCl4 injections

Abstract

Despite its long establishment and applicability in mice pain detection, the Mouse Grimace Scale still seems to be underused in acute pain detection during chronic experiments. However, broadening its applicability can identify possible refinement approaches such as cumulative severity and habituation to painful stimuli. Therefore, this study focuses on two main aspects: First, five composite MGS criteria were evaluated with two independent methods (the MoBPs algorithm and a penalized least squares regression) and ranked for their relative importance. The most important variable was used in a second analysis to specifically evaluate the context of pain after an i.p. injection (intervention) in two treatment groups (CCl4 and oil (control)) at fixed times throughout four weeks in 24 male C57BL/6 N mice. One hour before and after each intervention, video recordings were taken, and the MGS assessment was performed. In this study, the results indicate orbital tightening as the most important criterion. In this experimental setup, a highly significant difference after treatment between week 0 and 1 was found in the CCl4 group, resulting in a medium-sized effect (W = 62.5, p value < 0.0001, rCCl4 = 0.64). The oil group showed no significant difference (week 0 vs 1, W = 291.5, p value = 0.7875, rcontrol = 0.04). Therefore, the study showed that the pain caused by i.p. injections was only dependent on the applied substance, and no significant cumulation or habituation occurred due to the intervention. Further, the results indicated that the MGS system can be simplified.

Grimace scale assessment during Citrobacter rodentium inflammation and colitis development in laboratory mice

“…While the retrospective MGS revealed signs of pain alleviation in animals treated with buprenorphine, the lMGS did not ( 28 ). Furthermore, in a study investigating pain due to repeated intraperitoneal injections in mice, the authors showed elevated MGS in mice receiving CCl 4 , which is a model for liver fibrosis, but not in the control animals receiving the vehicle substance (oil only) ( 46 ). Very recently, Vezza et al showed increased facial pain expressions on day 4 after DSS treatment in a video-based retrospective analysis ( 47 ).…”

Grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats—A systematic review

“…This finding is in line with difficulties reported for a reliable assessment of whisker position ( 10 , 25 , 84 ), resulting in the decision to disregard this action unit. In this context, it is of interest that a recent study ranked the relative importance of MGS AUs based on two different mathematical approaches ( 128 ). While orbital tightening was identified as the best parameter, whisker change and nose bulge were the worst performing variables in this study focusing on pain responses to intraperitoneal CCl 4 injection ( 128 ).…”

“…In this context, it is of interest that a recent study ranked the relative importance of MGS AUs based on two different mathematical approaches ( 128 ). While orbital tightening was identified as the best parameter, whisker change and nose bulge were the worst performing variables in this study focusing on pain responses to intraperitoneal CCl 4 injection ( 128 ). The authors concluded that the findings suggest that the MGS can be simplified; however, they also emphasized that a model-specific assessment of the informative value of AUs might be necessary ( 128 ).…”

The grimace scale: a useful tool for assessing pain in laboratory animals

“…There are also efforts to further simplify the MGS in mice. Ernst et al developed a chronic liver fibrosis model by abdominal injection of tetrachloromethane (CCl 4 ) into mice over four weeks and evaluated the relative importance of the AUs of the MGS [ 36 ]. This study revealed that the tightening of the eyes has the most significant impact on the MGS score.…”