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

Abstract

Several studies suggested an informative value of behavioral and grimace scale parameters for the detection of pain. However, the robustness and reliability of the parameters as well as the current extent of implementation are still largely unknown. In this study, we aimed to systematically analyze the current evidence-base of grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats. The following platforms were searched for relevant articles: PubMed, Embase via Ovid, and Web of Science. Only full peer-reviewed studies that describe the grimace scale, burrowing, and/or nest building as pain parameters in the post-surgical phase in mice and/or rats were included. Information about the study design, animal characteristics, intervention characteristics, and outcome measures was extracted from identified publications. In total, 74 papers were included in this review. The majority of studies have been conducted in young adult C57BL/6J mice and Sprague Dawley and Wistar rats. While there is an apparent lack of information about young animals, some studies that analyzed the grimace scale in aged rats were identified. The majority of studies focused on laparotomy-associated pain. Only limited information is available about other types of surgical interventions. While an impact of surgery and an influence of analgesia were rather consistently reported in studies focusing on grimace scales, the number of studies that assessed respective effects was rather low for nest building and burrowing. Moreover, controversial findings were evident for the impact of analgesics on post-surgical nest building activity. Regarding analgesia, a monotherapeutic approach was identified in the vast majority of studies with non-steroidal anti-inflammatory (NSAID) drugs and opioids being most commonly used. In conclusion, most evidence exists for grimace scales, which were more frequently used to assess post-surgical pain in rodents than the other behavioral parameters. However, our findings also point to relevant knowledge gaps concerning the post-surgical application in different strains, age levels, and following different surgical procedures. Future efforts are also necessary to directly compare the sensitivity and robustness of different readout parameters applied for the assessment of nest building and burrowing activities.

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

“…Over the last years, pain and severity assessment has come into focus. Several methods such as burrowing, nesting, or the MGS were used to elucidate their possible usage in pain assessment in mice ( 21 ). The MGS has been applied in different mouse models to detect pain after vasectomy ( 35 ), thoracotomy ( 36 ) during the development of neuropathic pain, in multiple sclerosis, or in a model for sickle cell disease ( 37 – 39 ).…”

“…The scoring of facial expressions has been shown as a good parameter for the detection of postoperative pain in mice, and the so-called mouse grimace scale (MGS) is a frequently applied method in laboratory animal science ( 20 ). The MGS was established and widely used to assess pain in mice after laparotomy ( 21 ). The MGS scores the five facial action units, namely, orbital tightening, nose bulge, cheek bulge, ear position, and whisker change, and higher scores are indicative of pain ( 20 ).…”

A novel animal model of neuropathic corneal pain–the ciliary nerve constriction model

“…Various tests have been utilized to assess changes in pain response, spontaneous pain, and anxiety-like and depression-like behavior ( Palazzo et al, 2021 ). We assessed spontaneous pain (palpebral opening; Akintola et al, 2017 ; Aulehner et al, 2022 ), anxiety-like behavior (OF test), and depression-like behavior (nesting behavior; Gallo et al, 2020 ; Aulehner et al, 2022 ). We noted a significant difference in the palpebral opening following constriction.…”

Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents

“…All observations were made and diligently documented on a shared data sheet by blinded scorers/observers (E.P.-M. and A.C.-V. or J.C.-S.; an example of the “postoperative monitoring form” is provided in Supplementary Information S3 ). To ensure consistency and reproducibility, a scoresheet was designed, including several indicators related to general condition, nutritional and hydration status, spontaneous behavior, and surgery-related parameters, as well as compensatory measures, as detailed in Table 4 [ 15 , 17 , 20 , 21 , 22 , 39 , 40 ]. Overall, these welfare indicators were carefully chosen based on our experience with these specific surgical procedures and their relevance, ease of recognition, reliability, and effectiveness in providing accurate assessment of welfare [ 17 ].…”

“…Secondly, we use a combination of cyanoacrylate tissue adhesive and UV light-curing resin, which significantly reduces surgery time, improves wound healing, and reduces the postoperative recovery period, with a near 100% success rate. Thirdly, we have designed a customized welfare assessment scoresheet to monitor animals undergoing long-term cannula implantation, including indicators that accurately and effectively reflect animals’ well-being for this particular surgery [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. By implementing all the improvements, we evidenced a positive impact on animal welfare, the reduction in the number of animals used, and the quality of the experimental data, all of which align with the “refinement” and “reduction” principles of the 3Rs [ 13 ].…”