Development and validation of a cynomolgus macaque grimace scale for acute pain assessment

Abstract

Cynomolgus macaques may undergo surgical procedures for scientific and veterinary purposes. Recognition and assessment of pain using validated tools is a necessary first step for adequately managing pain in these primates. Grimace scales are one means of assessing the occurance of acute pain using action units such as facial expressions and posture. The aim of this study was to create and validate a Cynomolgus Macaque Grimace Scale (CMGS). Cynomolgus macaques (n = 43) were video recorded before and after a surgical procedure. Images were extracted from videos at timepoints at which breakthrough pain might be expected based on analgesic pharmacokinetics. Using the CMGS images were scored by 12 observers blinded to animal identification, times, and conditions. To validate the tool, detailed behavioral analyses emphasizing changes to baseline activity ethograms were compared to grimace scores. Four action units were identified related to potential pain including orbital tightening, brow lowering, cheek tightening, and hunched posture. The CMGS tool was found to have moderate inter- (ICCaverage action unit mean ± SD: 0.67 ± 0.28) and good intra- (ICCsingle mean ± SD: 0.79 ± 0.14) observer reliability. Grimace scores increased significantly (p < 0.0001) in the first four post-operative timepoints compared to baseline, correlating with behavioral findings (rho range = 0.22–0.35, p < 0.001). An analgesic intervention threshold was determined and should be considered when providing additional pain relief. The CMGS was shown to be a reliable and valid tool; however, more research is needed to confirm external validity. This tool will be highly valuable for refining analgesic protocols and acute peri-procedural care for cynomolgus macaques.

Effect of the observer’s gender bias monitoring acute pain using a validated behavior scale in castrated piglets

“…Contrary to our results, previous research reported observer's gender bias in whole-body behavior pain scales for cats 34,62 and dogs 62 , as well as macaque 13 , sow 28 , and donkey 23 grimace scales. In surveys of veterinarians' attitudes, women assigned higher pain levels than men for different surgical procedures in dogs and cats [52][53][54] .…”

“…In the last 30 years, scientists created grimace scales to assess pain in a wide variety of mammals, such as humans [10][11][12] , macaques 13 , mouses 14 , rats 15 , rabbits 16 , cats 17 , horses [18][19][20][21] , donkeys 22,23 , ferrets 24 , sheep 25,26 , and pigs 27,28 . Several pain scales have also been developed considering the whole-body behavior in non-human mammals, such as rats 29 , rabbits 30 , cats [31][32][33][34] , dogs 35 , horses 19,21,36,37 , donkeys 38 , cattle 39,40 , sheep 41,42 , goats 43 , and pigs 44,45 .…”

“…Additionally, women farms and veterinarians had different perceptions of pain than men when asked about painful procedures and diseases in bovines [55][56][57][58] , equines 59,60 , and swine 61 . Speci cally for the pain-altered behavior scales, the observers' gender impacted grimace scales for macaques 13 , sows 28 , and donkeys 23 , as well as wholebody behavioral pain scales in cats 34,62 and dogs 62 . Such studies suggest that the observers' gender might also contribute to oligoanalgesia or untreated pain 63 .…”

Development of a novel primate welfare assessment tool for research macaques

“…The main difference is that the EWAG focuses on assessing welfare at the individual level and monitoring cumulative suffering over time based on research use, whereas the PWAT is focused on assessing the overall primate behavioural management programme. Primates in research are used for more long-term studies compared to other research species, further emphasising the importance of a multifaceted approach to assessing welfare over time and considering cumulative suffering (Honess & Wolfensohn 2010 ; Paterson et al 2023 ). Using a broader tool such as the PWAT could help identify gaps in the primate management programme that could result in animal-based indicators of poor welfare or cumulative suffering, while implementing a purely animal-based measure of welfare, such as the EWAG, could be used to monitor specific at-risk animals based on procedural severity and cumulative use, which could then be used to make decisions on humane endpoints (Honess & Wolfensohn 2010 ; Nunamaker et al 2021 ).…”

Review of Environmental and Health Factors Impacting Captive Common Marmoset Welfare in the Biomedical Research Setting

“…The identification and management of pain, whether spontaneous, perioperative, or related to research manipulations, is key to optimizing the welfare of marmosets engaged in biomedical research. The development and validation of a pain scoring system such as that described for cynomolgus macaques in Paterson et al would enhance the ability of marmoset users to adequately manage perioperative and spontaneous pain in marmosets [ 42 ]. The author encourages the use of a facility-specific pain assessment tool, especially for postoperative pain management, that can be updated as more evidence-based guidelines are published.…”