Effect of topical vapocoolant spray on perioperative pain response of unweaned calves to ear tagging and ear notching.

OBJECTIVE: To evaluate the efficacy of a vapocoolant spray to provide local anaesthesia for calves during ear tagging and ear notching. STUDY DESIGN: Randomized study. ANIMALS: Twenty Black Angus calves aged 4-16 weeks old. METHODS: Temperature validation studies using thermocouples and a temperature data logger were conducted on dead and live tissue to determine optimal spray distance and duration to achieve tissue anaesthesia (<10 °C). A behavioural trial was conducted to assess efficacy for ear tagging and ear notching. Calves (n = 20) were randomly assigned to the vapocoolant spray (VS) or the water spray (WS) group. A 3 second spray was administered from 10 cm to both sides of the ear immediately prior to ear tagging and ear notching. A numerical rating scale (NRS) was used to score behavioural response to each procedure, with responses categorized from 0 (no response) to 3 (severe). RESULTS: Temperature and tissue validation studies indicated that a vapocoolant spray reduced dead and live tissue temperature to below nociceptive threshold levels (10 °C) for 10-16 seconds. Univariate analysis indicated that ear notching was more painful than ear tagging [odds ratio (OR) = 19.2, 95% confidence interval (CI): 5.34-68.99, p < 0.001]. When adjusted for the multivariate model, there was a significant effect of treatment, with WS calves showing higher pain response scores than VS calves (OR = 4.08, 95% CI: 1.34-12.42, p = 0.011). Ear notching resulted in greater pain response scores than ear tagging (OR = 23.19, 95% CI: 6.18-87.05, p < 0.001). CONCLUSIONS: and clinical relevance Vapocoolant spray induced local anaesthesia and significantly reduced the pain response to ear tagging and ear notching in calves. Ear notching is more painful than ear tagging. Cryoanaesthesia is an effective option for reducing the perioperative pain associated with these simple husbandry procedures.

Local cryoanalgesia is effective for tail-tip biopsy in mice.

Tail-tip biopsy for genotyping of genetically modified mice older than 21 d typically is performed by using isoflurane anesthesia. Isoflurane-induced changes in behavior and metabolism can result in unexpected complications and death. We investigated whether cryoanalgesia by using ethylene chloride spray would be an effective local anesthetic for tail-tip biopsies in mice. C57BL/6J mice were allocated randomly into 4 groups (n = 10 each) to receive isoflurane anesthesia with tail biopsy, ethylene chloride spray on the tip of the tail before biopsy, ethylene chloride spray without biopsy, or no treatment. Blood glucose was measured periodically in both groups undergoing tail biopsy, and the tail-pinch assay was performed in all mice that received ethylene chloride spray. Body weight, water, and food intake were measured daily for 2 wk. In both groups undergoing tail biopsy, blood glucose levels at 15 min were significantly higher than those after 2 min. This elevation was greater and more prolonged after 30 min in mice that received isoflurane compared with ethylene chloride spray. Tail-pinch latency at 20 min was greater than that after 2 min in all mice that received ethylene chloride spray. All mice gained weight, and there was no difference in food and water intake among groups. We conclude that ethylene chloride spray is an effective local anesthetic and a valuable alternative to isoflurane.

An in vivo platform for rapid high-throughput antitubercular drug discovery.

Treatment of tuberculosis, like other infectious diseases, is increasingly hindered by the emergence of drug resistance. Drug discovery efforts would be facilitated by facile screening tools that incorporate the complexities of human disease. Mycobacterium marinum-infected zebrafish larvae recapitulate key aspects of tuberculosis pathogenesis and drug treatment. Here, we develop a model for rapid in vivo drug screening using fluorescence-based methods for serial quantitative assessment of drug efficacy and toxicity. We provide proof-of-concept that both traditional bacterial-targeting antitubercular drugs and newly identified host-targeting drugs would be discovered through the use of this model. We demonstrate the model's utility for the identification of synergistic combinations of antibacterial drugs and demonstrate synergy between bacterial- and host-targeting compounds. Thus, the platform can be used to identify new antibacterial agents and entirely new classes of drugs that thwart infection by targeting host pathways. The methods developed here should be widely applicable to small-molecule screens for other infectious and noninfectious diseases.