Administration of Tramadol or Buprenorphine via the drinking water for post-operative analgesia in a mouse-osteotomy model

Abstract

Adequate analgesia is essential whenever pain might occur in animal experiments. Unfortunately, the selection of suitable analgesics for mice in bone-linked models is limited. Here, we evaluated two analgesics – Tramadol [0.1 mg/ml (T low ) vs. 1 mg/ml (T high )] and Buprenorphine (Bup; 0.009 mg/ml) – after a pre-surgical injection of Buprenorphine, in a mouse-osteotomy model. The aim of this study was to verify the efficacy of these opioids in alleviating pain-related behaviors, to provide evidence for adequate dosages and to examine potential side effects. High concentrations of Tramadol affected water intake, drinking frequency, food intake and body weight negatively in the first 2–3 days post-osteotomy, while home cage activity was comparable between all groups. General wellbeing parameters were strongly influenced by anesthesia and analgesics. Model-specific pain parameters did not indicate more effective pain relief at high concentrations of Tramadol. In addition, ex vivo high-resolution micro computed tomography (µCT) analysis and histology analyzing bone healing outcomes showed no differences between analgesic groups with respect to newly formed mineralized bone, cartilage and vessels. Our results show that high concentrations of Tramadol do not improve pain relief compared to low dosage Tramadol and Buprenorphine, but rather negatively affect animal wellbeing.

Early pH Changes in Musculoskeletal Tissues upon Injury—Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

“…For each investigation time point of the in vivo study, the pH within the hematomas was measured over a time period of two hours with a measurement interval of 10 s. For the time point 4 h after injury, the animals were kept in anesthesia until finalization. For all other time points, the animals recovered from anesthesia, were allowed normal activity and were treated with analgesia (Tramadolhydrochloride, Grünenthal, Aachen, Germany) that is optimized for this intervention for the other time points [63], before being anesthetized again for pH measurement. The last 30 min of the measurement were used for the evaluation of the pH values at the respective time points.…”

Spatial Distribution of Macrophages During Callus Formation and Maturation Reveals Close Crosstalk Between Macrophages and Newly Forming Vessels

“…Following skin closure, mice received pre-warmed NaCl (0.2 ml) s.c., permeable wound dressing spray and could recover from anesthesia in their home cage under infrared light and close monitoring. Tramadol was applied via the drinking water (0.1 mg/ml; Grünenthal, Germany) for 3 days after osteotomy (33). Given the short time period of treatment, we expect no negative influence of the analgetics on the fracture healing outcome (33).…”

HIF-stabilization prevents delayed fracture healing

“…PFA-fixed femora were treated with an ascending sucrose solution (10%, 20%, 30%) for 24 h, respectively at 4°C. Scanning of 191 slices was performed after removal of the pins and external fixator with an isotropic voxel size of 10.5 μm (70 KVp, 114 μA; SCANCO µCT Viva 40), aligned scan axis along the diaphyseal axis of the femora and 3D reconstruction and analyses were performed using the provided software package as described previously and applying a fixed global threshold of 240 mg HA/cm 3 for the automatic 3D callus tissue analysis (56,98). Nomenclature and analysis were conducted in accordance with published recommendations (100).…”

“…Pictures were taken with a fluorescence microscope BZ 9000 (Keyence). Image analysis was performed with ImageJ (56,57,98).…”