Testing perioperative meloxicam analgesia to enhance welfare while preserving model validity in an inflammation-induced seizure model

Abstract

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.