Metamizole

Three male beagle dogs (mean age 18 months, mean weight 12.5 kg) were used for the study. All operations and measurements were performed under general anaesthesia using intravenous injections of ketamine hydrochloride (2.5 ml/10 kg; Ketavet 10%, Pfizer, Berlin, Germany) and xylazine hydrochloride (1 ml/10 kg; Xylavet 2%, Sanofi-Aventis, Budapest, Hungary) administered every 15 min. For pain control, Metamizole (1 ml/10 kg; Algopyrin, Sanofi-Aventis, Budapest, Hungary) was injected intramuscularly after completion of the operations and was continued for 3 days. To prevention infections, intramuscular injection of amoxicillin hydrochloride solution (150 mg/ml, 1 ml/10 kg, Pfizer, Berlin, Germany) was administered after surgery for 2 weeks.

All procedures, handling, and experiments of animals were conducted in accordance with international regulations and ethical standards as well as with the regulations of the Medical University of Vienna and were performed under the licenses approved by the Austrian Ministry of Science.
Data from 11 C57BL/6 adult male mice (28–36 g) were included in this study. Subjects were grown from an in-house colony and housed accordingly to international/well-established standards. Implantation surgeries were conducted as previously described (Lasztoczi and Klausberger 2016 (link)). Mice were anesthetized with isoflurane (Forane, AbbVie; induction) and mounted on a stereotaxic frame (Kopf instrument). Two screws were implanted above the cerebellum, serving as ground and reference, respectively. Two additional screws were driven above the prefrontal cortex. Supported by the four screws, a custom-made plastic head plate (Mr. Asenov; IST, Vienna) was implanted. Coordinates aiming at the right dorsal hippocampus (lateral, 1.3 mm; posterior, 1.9 mm; Franklin and Paxinos 2008 ) were calculated, and the skull above was marked for future reference. Mice were injected with Metamizole (15 µl Novalgin, Sanofi; 25 mg /100 g body weight) and singly housed.

Metamizole (Met, 500 mg/kg; SANOFI, Germany) was dissolved in water for injection and administered intraperitoneally (ip) preemptively 16 and 1 h before CCI and then twice a day for 7 days. The dose of Metamizole was chosen based on our previous research [23 (link)] and the available literature [27 (link), 28 (link)]. The control group received vehicle (water for injection) according to the same schedule. Before drug injections, the baseline behaviors of the animals were determined using von Frey and cold plate tests. No adverse side effects of Metamizole treatment were observed during the experiments.