The “WWHow” Concept for Prospective Categorization of Post-operative Severity Assessment in Mice and Rats

Abstract

The prospective severity assessment in animal experiments in the categories' non-recovery, mild, moderate, and severe is part of each approval process and serves to estimate the harm/benefit. Harms are essential for evaluating ethical justifiability, and on the other hand, they may represent confounders and effect modifiers within an experiment. Catalogs and guidelines provide a way to assess the experimental severity prospectively but are limited in adaptation due to their nature of representing particular examples without clear explanations of the assessment strategies. To provide more flexibility for current and future practices, we developed the modular Where-What-How (WWHow) concept, which applies findings from pre-clinical studies using surgical-induced pain models in mice and rats to provide a prospective severity assessment. The WWHow concept integrates intra-operative characteristics for predicting the maximum expected severity of surgical procedures. The assessed severity categorization is mainly congruent with examples in established catalogs; however, because the WWHow concept is based on anatomical location, detailed analysis of the tissue trauma and other intra-operative characteristics, it enables refinement actions, provides the basis for a fact-based dialogue with authority officials and other stakeholders, and helps to identify confounder factors of study findings.

Behavioral outcome measures in preclinical rodent models for postoperative pain: A protocol for a systematic review and quantitative meta-analysis

“…The re nement actions directly investigating postoperative pain can, for example, de ne intervention-speci c minimum required observation time and de nitions for time windows for drug treatment in the different models for postoperative pain. This would directly address and at best even reduce the suffering of animals in studies of postoperative pain, as evidence-based time courses can be relied upon and might reduce the number of animals required due to more homogenious dataHere, the SR results can also be used for evidence-based animal welfare science because surgical interventions are part of animal experimentation projects in a large number of cases, and detailed knowledge of the different pain behaviors and their in uence on welfare is necessary [50].…”

Pain Research and Treatment: Policy Implications

“…Pain and discomfort are main considerations for animal welfare policy in research, commercial, and entertainment settings (Simmonds, 2018). As the majority of preclinical research subjects are rodents, there are multiple guidelines regarding their care and use across the globe with ongoing efforts to categorize and quantify experimental processes, with particular emphasis on the minimization of pain and distress (for example, see Tappe-Theodor et al, 2022). Despite scientific journals routinely including statements attesting to the compliance of the animal studies with international regulations, there are often discrepancies in their implementation and an apparent lack of oversight (Diaz, 2020).…”

Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents

“…Secondly, we use a combination of cyanoacrylate tissue adhesive and UV light-curing resin, which significantly reduces surgery time, improves wound healing, and reduces the postoperative recovery period, with a near 100% success rate. Thirdly, we have designed a customized welfare assessment scoresheet to monitor animals undergoing long-term cannula implantation, including indicators that accurately and effectively reflect animals’ well-being for this particular surgery [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. By implementing all the improvements, we evidenced a positive impact on animal welfare, the reduction in the number of animals used, and the quality of the experimental data, all of which align with the “refinement” and “reduction” principles of the 3Rs [ 13 ].…”