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 Δ latency 10 h). Analgesic treatment using the anti-inflammatory drug carprofen (5 mg/kg bodyweight) decreased latency of burrowing after surgery (mean Δ latency 5.5 h) to the level found in mice that had been anesthetized (mean Δ latency 5.4 h) or had received anesthesia and analgesia (mean Δ 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 anesthesia/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.

AimsCoronary late stent thrombosis, a rare but devastating complication, remains an important concern in particular with the increasing use of drug-eluting stents. Notably, pathological studies have indicated that the proportion of uncovered coronary stent struts represents the best morphometric predictor of late stent thrombosis. Intracoronary optical frequency domain imaging (OFDI), a novel second-generation optical coherence tomography (OCT)-derived imaging method, may allow rapid imaging for the detection of coronary stent strut coverage with a markedly higher precision when compared with intravascular ultrasound, due to a microscopic resolution (axial ∼10–20 µm), and at a substantially increased speed of image acquisition when compared with first-generation time-domain OCT. However, a histological validation of coronary OFDI for the evaluation of stent strut coverage in vivo is urgently needed. Hence, the present study was designed to evaluate the capacity of coronary OFDI by electron (SEM) and light microscopy (LM) analysis to detect and evaluate stent strut coverage in a porcine model.Methods and resultsTwenty stents were implanted into 10 pigs and coronary OFDI was performed after 1, 3, 10, 14, and 28 days. Neointimal thickness as detected by OFDI correlated closely with neointimal thickness as measured by LM (r = 0.90, P < 0.01). The comparison of stent strut coverage as detected by OFDI and SEM analysis revealed an excellent agreement (r = 0.96, P < 0.01). In particular, stents completely covered by OFDI analysis were also completely covered by SEM analysis. All incompletely covered stents by OFDI were also incompletely covered by SEM. Analyses of fibrin-covered stent struts suggested that these may rarely be detected as uncovered stent struts by OFDI. Importantly, optical density measurements revealed a significant difference between fibrin- and neointima-covered coronary stent struts [0.395 (0.35–0.43) vs. 0.53 (0.47–0.57); P < 0.001], suggesting that differences in optical density provide information on the type of stent strut coverage. The sensitivity and specificity for detection of fibrin vs. neointimal coverage was evaluated using receiver-operating characteristic analysis.ConclusionThe present study demonstrates that OFDI is a highly promising tool for accurate evaluation of coronary stent strut coverage, as supported by a high agreement between OFDI and light and electron microscopic analysis. Furthermore, our data indicate that optical density measurements can provide additional information with respect to the type of stent strut coverage, i.e. fibrin vs. neointimal coverage. Therefore, coronary OFDI analysis will provide important information on the biocompatibility of coronary stents.

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.

The moldable, synthetic calcium phosphates are safe and suitable bone graft substitutes with outcomes that are comparable to the control material.