No abstract

No abstract

No abstract

The low reliability of the preclinical study’s findings is of critical concern. The possible sources include poor experimental design and a lack of measures to reduce the risk of bias. In this study, we focused on anti-migraine drug discovery and a particular animal model with the aim to contribute to the elimination of these sources in future research. We performed a systematic search of controlled studies testing established migraine treatments in the model of trigeminovascular nociception (EMTVN) and meta-analysis for the main outcomes to estimate the overall effect sizes. In 13 studies reporting on 21 experiments, anti-migraine drugs significantly decreased trigeminovascular nociceptive traffic compared with a control intervention. Considering these effects biologically relevant, we used them in sample size calculation for future experiments. To refine the EMTVN and inform its users, we explored the impact of methodological features on the outcome and revealed several factors potentially impacting the results obtained in this model. We also assessed the internal validity of the included studies and found that the selection bias, particularly, the lack of randomisation, is likely a main source of bias. Based on our findings, we discuss the translational potential of the EMTVN and suggest what should be addressed for its improvement. We believe that this work highlights the importance of systematic reviews and meta-analyses as tools for design optimisation in animal research.

The main reasons for the low reliability of results from preclinical studies are the lack of prior sample size calculations and poor experimental design. Here, we demonstrate how the tools of meta-analysis can be implemented to tackle these issues. We conducted a systematic search to identify controlled studies testing established migraine treatments in the electrophysiological model of trigeminovascular nociception (EMTVN). Drug effects on the two outcomes, dural stimulation-evoked responses and ongoing neuronal activity were analysed separately using a three-level model with robust variance estimation.According to the meta-analysis, which included 21 experiments in rats reported in 13 studies, these drugs significantly reduced trigeminovascular nociceptive traffic, affecting both outcomes. Based on the estimated effect sizes and outcome variance, we provide guidance on sample sizes allowing to detect such effects with sufficient power in future experiments. Considering the revealed methodological features that potentially influence the results and the main source of statistical bias of the included studies, we discuss the translational potential of the EMTVN and the steps needed to improve it. We believe that the presented approach can be used for design optimization in research with other animal models and as such deserves further validation.