Weiß Edna, Pauletti Alberto, Egilmez Asya, Bröer Sonja
Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Koserstraße 20, 14195, Berlin, Germany.
Sci Rep. 2024 Dec 19;14(1):30563. doi: 10.1038/s41598-024-81925-7.
Despite the international effort to improve laboratory animal welfare through the 3R principles (Reduce, Refine, Replace), many scientists still fail to implement and report their assessment of pain and well-being, likely due to concerns regarding the potential effects of analgesics on experimental outcomes. This study aimed to determine whether refining our viral encephalitis model with perioperative analgesia could enhance well-being and recovery after intracerebral virus infection without impacting disease outcomes. We routinely use the Theiler's Murine Encephalomyelitis Virus (TMEV) model to study virus-induced epilepsy. Given the crucial role of immune cell activation in acute seizure development, we evaluated the effects of the non-steroidal anti-inflammatory drug (NSAID) meloxicam on inflammation, neurodegeneration, and neuronal cell proliferation at 7 days post-infection (dpi). Overall, the impact of virus infection on well-being was less severe than anticipated, and meloxicam treatment did not affect well-being or nest building behavior in TMEV-infected mice. Furthermore, meloxicam treatment did not influence key experimental readouts such as seizure burden, central inflammatory response, neurodegeneration, or neuronal proliferation within the hippocampus. Notably, animals experiencing seizures displayed heightened inflammatory responses and neurodegeneration, which were not influenced by meloxicam treatment. In summary, perioperative analgesia did not compromise key outcome measures such as seizure frequency, inflammation, and neurodegeneration or -regeneration in the TMEV model. However, it also did not add any significant benefits to well-being in the first week after intracranial injections.
尽管国际上努力通过3R原则（减少、优化、替代）来改善实验动物福利，但许多科学家仍未实施并报告他们对疼痛和健康状况的评估，这可能是由于担心镇痛药对实验结果的潜在影响。本研究旨在确定围手术期镇痛对我们的病毒性脑炎模型进行优化是否能在不影响疾病结果的情况下，提高脑内病毒感染后的健康状况和恢复能力。我们常规使用泰勒氏鼠脑脊髓炎病毒（TMEV）模型来研究病毒诱导的癫痫。鉴于免疫细胞激活在急性癫痫发作发展中的关键作用，我们评估了非甾体抗炎药美洛昔康在感染后7天（dpi）对炎症、神经退行性变和神经元细胞增殖的影响。总体而言，病毒感染对健康状况的影响不如预期严重，美洛昔康治疗对TMEV感染小鼠的健康状况或筑巢行为没有影响。此外，美洛昔康治疗并未影响关键的实验指标，如癫痫发作负担、中枢炎症反应、神经退行性变或海马体内的神经元增殖。值得注意的是，经历癫痫发作的动物表现出更高的炎症反应和神经退行性变，而这不受美洛昔康治疗的影响。总之，围手术期镇痛并未损害TMEV模型中的关键结果指标，如癫痫发作频率、炎症和神经退行性变或再生。然而，在颅内注射后的第一周，它也没有给健康状况带来任何显著益处。
