The study investigates the effects of perioperative meloxicam analgesia on welfare and experimental outcomes in mice with inflammation-induced seizures.
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 about the potential effects of analgesics on experimental outcomes. This study aimed to determine whether refining the viral encephalitis model with perioperative analgesia could improve well-being and recovery after intracerebral virus infection without affecting disease outcomes.
Researchers routinely use the Theiler’s Murine Encephalomyelitis Virus (TMEV) model to study virus-induced epilepsy. Given the pivotal role of immune cell activation in acute seizure development, the effects of the non-steroidal anti-inflammatory drug (NSAID) meloxicam on inflammation, neurodegeneration, and neuronal cell proliferation were evaluated at seven 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. The outcomes are significant for animal welfare discussions within experimental protocols.
Meloxicam treatment did not influence key experimental readouts such as seizure burden, central inflammatory response, neurodegeneration, or neuronal proliferation within the hippocampus. It was observed, though, heightened inflammatory responses and neurodegeneration occurred amid seizure activity; these remained unaffected by meloxicam treatment. The conclusion was drawn indicating perioperative analgesia did not compromise key outcome measures nor bring any significant benefits to well-being after intracranial injections.
More than a decade has passed since the enactment of Directive 2010/63/EU, which outlines protocols for protecting animals used in scientific research based on the principles of Replacement, Reduction, and Refinement (3Rs). These guidelines advocate for the replacement of animals with non-sentient alternatives whenever possible, the reduction of animal use, and the refinement of experimental methodologies to minimize pain and distress. Current inquiries reveal many scientists neglect reporting their analgesia management, with insufficient attention paid to improving the conduct of animal experiments.
Meloxicam was administered at 5 mg/kg during postoperative care, aiming to assess its capability of enhancing recovery and reducing morbidity without skewing experimental results. The evaluation methodologies included well-being scoring, nest-building performance, and weight development, performed on various experimental cohorts of inoculated and control mice.
Importantly, results from this study elucidated meloxicam did not influence the incidence or severity of seizures across treated groups. Seizures predominantly manifested between three and six dpi, with no significant differences detected between meloxicam-treated and untreated cohorts. The consistent outcomes suggest meloxicam treatment does not appreciably modify inflammatory responses or neuronal loss after viral infections.
The findings align with existing literature asserting the need for improved animal welfare methods during procedures requiring invasive actions like craniotomies—where pain experiences, though difficult to quantify, remain evident. Yet, researchers often grapple with the fear of analgesic effects interfering with experimental outcomes, creating hesitancy for implementing welfare improvements.
This study’s limitations point to inherent subjectivity surrounding assessment methodologies for pain and stress, with proponents arguing for more objective measures, such as the Mouse Grimace Scale (MGS). Such advancements could bolster adherence to welfare guidelines and yield enhanced experimental validity.
Overall, the current research underpins the assertion of thorough pain management and welfare protocols during experimentation, emphasizing the necessity of continual development toward improved guidelines for the care of laboratory animals. The lack of perceived benefits from meloxicam stresses the point for future evaluations exploring various analgesic applications and their consequential impact across male and female subjects.
Discussions surrounding the broader implementation of welfare measures, the subsequent reporting of experimentation processes, and reinforcement of guidelines will be imperative for fostering integrity and validation within scientific research.
