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A model-specific simplification of the Mouse Grimace Scale based on the pain response of intraperitoneal CCl4
Lisa Ernst1, Stefan Bruch1, Marcin Kopaczka2
1Faculty of Medicine, Institute for Laboratory Animal Science and Experimental Surgery, RWTH Aachen University, Aachen, Germany.
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.
Insights
The Mouse Grimace Scale (MGS) effectively detects acute pain in mice, with orbital tightening being the key indicator. This study simplifies MGS use in chronic experiments, finding pain depends solely on the injected substance.
Area of Science:
- Veterinary Science
- Animal Behavior
- Pain Research
Background:
- The Mouse Grimace Scale (MGS) is established for mouse pain detection but underutilized in chronic experiments.
- Refinements like assessing cumulative severity and habituation are possible.
- This study evaluates MGS criteria importance and applicability in chronic pain models.
Purpose of the Study:
- To rank the importance of five composite Mouse Grimace Scale criteria using statistical methods.
- To assess the Mouse Grimace Scale's utility in detecting acute pain following intraperitoneal injections in a chronic experimental setup.
- To determine if pain perception shows cumulative effects or habituation over time.
Main Methods:
- Evaluated five composite MGS criteria using the MoBPs algorithm and penalized least squares regression.
- Administered intraperitoneal injections of CCl4 or oil (control) to male C57BL/6N mice over four weeks.
- Recorded MGS assessments before and after interventions, analyzing video recordings.
Main Results:
- Orbital tightening was identified as the most significant MGS criterion.
- The CCl4 group showed a significant difference in pain response between week 0 and week 1 (p < 0.0001).
- No significant cumulative effects or habituation to pain stimuli were observed; pain was substance-dependent.
Conclusions:
- The Mouse Grimace Scale can be simplified by focusing on key indicators like orbital tightening.
- Acute pain from intraperitoneal injections is primarily determined by the injected substance, not cumulative exposure.
- MGS is a valuable tool for refining pain assessment in chronic mouse studies.
