The composition and initial evaluation of a grimace scale in ferrets after surgical implantation of a telemetry probe

Abstract

Reliable recognition of pain is difficult in ferrets as many currently available parameters are non-specific, inconsistent and/or impractical. Grimace scales have successfully been applied to assess pain in different animal species and might also be applicable to ferrets. To compose a Ferret Grimace Scale (FGS), we studied the facial musculature of ferrets and compared lateral photographs of 19 ferret faces at six time points before and after intraperitoneal telemetry probe implantation. We identified the Action Units (AUs) orbital tightening, nose bulging, cheek bulging, ear changes and whisker retraction as potential indicators of pain in ferrets. To evaluate whether these AUs could reliably be used to identify photographs taken before and after surgery, the photographs were scored 0, 1 or 2 (not, moderately or obviously present) by 11 observers that were blinded to the treatment and timing of the photographs. All AU-scores assigned to the photographs taken five hours after surgery were significantly higher compared to their time-matched baseline scores. Further analysis using the weights that were obtained using a Linear Discriminant Analysis revealed that scoring orbital tightening alone was sufficient to make this distinction with high sensitivity, specificity and accuracy. Including weighted scores for nose bulging, cheek bulging and ear change did not change this. As these AUs had more missing values than orbital tightening, their descriptions should be re-evaluated. Including whisker retraction, which had a negative weight, resulted in lower accuracy and should therefore in its current form be left out of the FGS. Overall, the results of this study suggest that the FGS and the AU orbital tightening in particular could be useful in a multifactorial pain assessment protocol for ferrets. However, before applying the FGS in practice, it should be further validated by incorporating more time points before and after applying (different) painful stimuli, and different levels of analgesia.

Evaluating analgesic efficacy and administration route following craniotomy in mice using the grimace scale

“…The evaluation of different drugs, routes of administration, testing sites, mouse sex and mouse strain using the MGS as a primary output demonstrate the reliability of the MGS, but also point toward the CD1 mouse strain as an optimal choice for analgesic drug screening using this assay. The grimace scales have shown excellent consistency in pain detection among rodents and other species 11,12,14,17,21 , however no single study has ever compared generalizability among experimenters, testing sites or pharmacological effects. Both the MGS and RGS (rat grimace scale) show robust inter-rater reliability, but these analyses have largely been conducted among individuals within the same test site and coding the same set of images.…”

“…Each feature is given a score of 0 (not present), 1 (moderate) or 2 (severe), which can be scored with remarkably high reliability and accuracy. Although the grimace scale has been readily evaluated in mice 11,14,15 and rats 12,16 , other grimace scales have been developed to capture 'pain faces' in horses 17 , cats 18 , rabbits 19 , sheep 20 and ferrets 21 , which have helped to evaluate postoperative pain across species.…”

Can grimace scales estimate the pain status in horses and mice? A statistical approach to identify a classifier

“…An automatic monitoring system, based on a classification paradigm, was also proposed for the pain recognition in patients with shoulder pain [ 9 – 11 ]: with this aim a shared database was created and consisted of 200 video sequences containing spontaneous facial expressions of pain and associated pain frame-by-frame scores [ 12 ]. A classifier for monitoring facial expressions could increase the reliability, sensitivity, and precision of the research into the relationship between facial signs and experiences of pain, and so lead to new insights and diagnostic methods [ 13 – 15 ]. Facial expressions have been investigated for pain assessment in several non-human mammal species, including mice [ 16 – 18 ] and horses [ 19 – 21 ].…”

“…The Mouse Grimace Scale (MGS) [ 16 ] is the sum of five facial features (FAUs): orbital tightening, nose bulge, cheek bulge, ear position, and whisker change. Both HGS and MGS have been partially validated for pain assessment under different conditions [ 15 – 19 , 21 , 22 ]. HGS was applied in post-surgical condition [ 19 ] as well as orthopaedic pain [ 20 ]; MGS was used in experimental models of pain [ 16 ] and post-surgery [ 18 , 23 ].…”

Development and validation of a multidimensional composite pain scale for Rabbit (CANCRS) in a clinical environment

“…However, there is no validated equivalent for rabbits and the only existing pain scale for this species is the Rabbit Grimace Scale (RbtGS) 13 , which uses changes in facial expression to quantify pain. Grimace scales have been developed and validated in several species, such as Horse 14 , Sheep 15 , Ferrets 16 and laboratory small rodents 17,18 .…”