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

Abstract

Most research laboratories abide by guidelines and mandates set by their research institution regarding the administration of analgesics to control pain during the postoperative period. Unfortunately, measuring pain originating from the head is difficult, making adequate decisions regarding pain control following stereotaxic surgery problematic. In addition, most postsurgical analgesia protocols require multiple injections over several days, which may cause stress and distress during a critical recovery period. Here we sought to (1) assess the degree of postoperative pain following craniotomy in mice, (2) compare the efficacy of three common rodent analgesics (carprofen, meloxicam and buprenorphine) for reducing this pain and (3) determine whether the route of administration (injected or self-administered through the drinking supply) influenced pain relief post-craniotomy. Using the mouse grimace scale (MGS), we found that injectable analgesics were significantly more effective at relieving post-craniotomy pain, however, both routes of administration decreased pain scores in the first 24 h postsurgery. Specifically, buprenorphine administered independently of administration route was the most effective at reducing MGS scores, however, female mice showed greater sensitivity to carprofen when administered through the water supply. Although it is necessary to provide laboratory animals with analgesics after an invasive procedure, there remains a gap in the literature regarding the degree of craniotomy-related pain in rodents and the efficacy of alternative routes of administration. Our study highlights the limitations of administering drugs through the drinking supply, even at doses that are considered to be higher than those currently recommended by most research institutions for treating pain of mild to moderate severity.

Use of the Rat Grimace Scale to Evaluate Visceral Pain in a Model of Chemotherapy-Induced Mucositis

“…Furthermore, the rat strain used may have impacted on the ability to accurately score facial features. Previous research has implied that detection of grimace facial features in dark-colored animals is impaired [33,34]. This may however be as a result of poor achievement of background contrast, rather than the pigmentation of the animal per se.…”

The Use of Analgesics during Vaccination with a Live Attenuated Yersinia pestis Vaccine Alters the Resulting Immune Response in Mice

“…These differences that are observed in group-housed male mice are likely not reflective of higher mammalian disease models. Previous studies demonstrated differences between males and females with regard to pain and analgesia, but these data vary based upon species of animal, pain model used, and type of analgesic administered [130][131][132][133][134][135][136][137][138][139][140][141]. Thus, sex differences can also be confounding variables when examining pain and analgesia as well.…”

Differential modulation of thermal preference after sensitization by optogenetic or pharmacological activation of heat-sensitive nociceptors

“…DeepLabCut is an open-source animal tracking program that uses deep neural networks to recognize labelled points in videos. 16 DeepLabCut’s tracking algorithm was trained to recognize the mouse’s centre, labelled as visually close to EthoVision’s calculated centre as possible, with 200 distinct marked reference frames. All other settings were left as default as specified in the setup protocol.…”

“…These concerns have led to increased usage of unconditioned or non-evoked behavioral responses with the aim of capturing endogenous indicators of spontaneous or ongoing pain. 11 Such measures include operant assays, the Mouse Grimace Scale, 16 , 17 automated behavioral tracking, 11 weight-bearing or gait analysis, nesting or burrowing behavior, ultrasonic vocalizations, and free-choice temperature preference. 18 , 19 Along with increased adoption of assays for spontaneous pain, there has also been an increase in the automation of data collection.…”