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An impaired intestinal epithelial barrier is thought to be a major factor in the pathogenesis of human inflammatory bowel disease (IBD). IBD is frequently investigated by inducing a damaged barrier in murine models of colitis. This can be done by feeding mice with dextran sulfate sodium (DSS) polymers in their drinking water. Refinement measures should focus on alleviating unnecessary suffering during this probably painful condition. Appropriate parameters are needed to decide when to terminate the experiments. Our aim was to investigate whether a change in burrowing behaviour is a sensitive measure of animal welfare in murine models of colitis. Acute colitis was induced in C57BL/6 mice with 2.0% DSS over nine days. The burrowing test is based on the species-typical behaviour of mice to spontaneously displace items from tubes within their home cage. As a burrowing apparatus, a water bottle (250 mL, 150 mm length, 55 mm diameter) filled with 138–142 g of pellets of the animal’s diet was used. The presence of intestinal inflammation as a result of acute DSS-induced colitis was confirmed by a decrease in body weight, colon length and an increase of murine endoscopic index of colitis severity, histological score and spleen weight in the group receiving DSS as compared with the control group. An onset of intestinal inflammation correlated with a significant decrease in burrowing behaviour ( P

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a manageable size and relatively easy to house. These factors, together with the availability of a wealth of spontaneous and experimentally induced mutants, make laboratory mice ideally suited to a wide variety of research areas. In cardiovascular, pharmacological and toxicological research, accurate measurement of parameters relating to the circulatory system of laboratory animals is often required. Determination of heart rate, heart rate variability, and duration of PQ and QT intervals are based on electrocardiogram (ECG) recordings. However, obtaining reliable ECG curves as well as physiological data such as core body temperature in mice can be difficult using conventional measurement techniques, which require connecting sensors and lead wires to a restrained, tethered, or even anaesthetized animal. Data obtained in this fashion must be interpreted with caution, as it is well known that restraining and anesthesia can have a major artifactual influence on physiological parameters1, 2. Radiotelemetry enables data to be collected from conscious and untethered animals. Measurements can be conducted even in freely moving animals, and without requiring the investigator to be in the proximity of the animal. Thus, known sources of artifacts are avoided, and accurate and reliable measurements are assured. This methodology also reduces interanimal variability, thus reducing the number of animals used, rendering this technology the most humane method of monitoring physiological parameters in laboratory animals3, 4. Constant advancements in data acquisition technology and implant miniaturization mean that it is now possible to record physiological parameters and locomotor activity continuously and in realtime over longer periods such as hours, days or even weeks3, 5. Here, we describe a surgical technique for implantation of a commercially available telemetry transmitter used for continuous measurements of core body temperature, locomotor activity and biopotential (i.e. onelead ECG), from which heart rate, heart rate variability, and PQ and QT intervals can be established in freeroaming, untethered mice. We also present pre-operative procedures and protocols for post-operative intensive care and pain treatment that improve recovery, well-being and survival rates in implanted mice5, 6.

Detection of persistent pain of a mild-to-moderate degree in laboratory mice is difficult because mice do not show unambiguous symptoms of pain or suffering using standard methods of short-term observational or clinical monitoring. This study investigated the potential use of burrowing performance — a spontaneous and highly motivated behavior — as a measure of post-operative pain in laboratory mice. The influence of minor surgery on burrowing was investigated in adult C57BL/6J mice of both genders in a modified rodent burrowing test (displacement of food pellets from a pellet-filled tube) within the animal’s home cage. Almost all (98%) healthy mice burrowed (mean latency 1.3 h, SEM 0.5 h). After surgery without pain treatment, latency of burrowing was significantly prolonged (mean ∆ latency 10 h). Analgesic treatment using the anti-inflammatory drug carprofen (5 mg/kg bodyweight) decreased latency of burrowing after surgery (mean ∆ latency 5.5 h) to the level found in mice that had been anaesthetised (mean ∆ latency 5.3 h) or had received anaesthesia and analgesia (mean ∆ latency 4.6 h). Analgesia during surgery was associated with a significantly earlier onset of burrowing compared to surgery without pain treatment. A distinct gradation in burrowing performance was found ranging from the undisturbed pre-operative status to the intermediate level following anaesthesia/analgesia and surgery with analgesia, to the pronounced prolongation of latency to burrow after surgery without pain relief. In conclusion, post-surgical impairment of general condition, probably mainly attributable to pain, can be conveniently assessed in laboratory mice on the basis of the burrowing test.

Isoflurane is currently the most common volatile anaesthetic used in laboratory mice, whereas in human medicine the more modern sevoflurane is often used for inhalation anaesthesia. This study aimed to characterize and compare the clinical properties of both anaesthetics for inhalation anaesthesia in mice. In an approach mirroring routine laboratory conditions (spontaneous breathing, gas supply via nose mask, preventing hypothermia by a warming mat) a 50 min anaesthesia was performed. Anaesthetics were administered in oxygen as carrier gas at standardized dosages of 1.5 minimum alveolar concentrations, which was 2.8% for isoflurane and 4.9% for sevoflurane. Both induction and recovery from anaesthesia proceeded quickly, within 1–2 min. During anaesthesia, all reflex testing was negative and no serious impairment of vital functions was found; all animals survived. The most prominent side-effect during anaesthesia was respiratory depression with hypercapnia, acidosis and a marked decrease in respiration rate. Under anaesthesia, heart rate and core body temperature remained within the normal range, but were significantly increased for 12 h after anaesthesia. Locomotor activity, daily food and water consumption and body weight progression showed no abnormalities after anaesthesia. No significant difference was found between the two anaesthetics. In conclusion, isoflurane and sevoflurane provided an equally reliable anaesthesia in laboratory mice.

Background The laboratory mouse is commonly used as a sophisticated model in biomedical research. However, experiments requiring major surgery frequently lead to serious postoperative complications and death, particularly if genetically modified mice with anatomical and physiological abnormalities undergo extensive interventions such as transmitter implantation. Telemetric transmitters are used to study cardiovascular physiology and diseases. Telemetry yields reliable and accurate measurement of blood pressure in the free-roaming, unanaesthetized and unstressed mouse, but data recording is hampered substantially if measurements are made in an exercising mouse. Thus, we aimed to optimize transmitter implantation to improve telemetric signal recording in exercising mice as well as to establish a postoperative care regimen that promotes convalescence and survival of mice after major surgery in general. Results We report an optimized telemetric transmitter implantation technique (fixation of the transmitter body on the back of the mouse with stainless steel wires) for subsequent measurement of arterial blood pressure during maximal exercise on a treadmill. This technique was used on normal (wildtype) mice and on transgenic mice with anatomical and physiological abnormalities due to constitutive overexpression of recombinant human erythropoietin. To promote convalescence of the animals after surgery, we established a regimen for postoperative intensive care: pain treatment (flunixine 5 mg/kg bodyweight, subcutaneously, twice per day) and fluid therapy (600 μl, subcutaneously, twice per day) were administrated for 7 days. In addition, warmth and free access to high energy liquid in a drinking bottle were provided for 14 days following transmitter implantation. This regimen led to a substantial decrease in overall morbidity and mortality. The refined postoperative care and surgical technique were particularly successful in genetically modified mice with severely compromised physiological capacities. Conclusion Recovery and survival rates of mice after major surgery were significantly improved by careful management of postoperative intensive care regimens including key supportive measures such as pain relief, administration of fluids, and warmth. Furthermore, fixation of the blood pressure transmitter provided constant reliable telemetric recordings in exercising mice.