The Influence of Metoclopramide on Trigeminovascular Nociception: Possible Anti-migraine Mechanism of Action

Dolgorukova, Antonina; Osipchuk, A. V.; Murzina, Anna A; Sokolov, Alexey Y.

doi:10.1016/j.neuroscience.2019.11.026

Cited by 8 publications

(9 citation statements)

References 80 publications

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“…In one study (Akerman & Romero‐Reyes, 2019), the effects of the drugs on the evoked activity were reported in absolute values, and the authors kindly provided the data expressed as % changes from baseline as well as numbers of units with C‐fibre inputs. Dolgorukova et al (2020) reported medians and interquartile ranges, and means with SDs were obtained from the authors. The corresponding authors of the remaining four studies did not respond to our data request.…”

Section: Resultsmentioning

confidence: 99%

Meta‐analysis of the effects of anti‐migraine therapeutics in the rat trigeminovascular nociception model as a tool for design optimization

Dolgorukova

Protsenko

Isaeva

et al. 2023

Eur J of Neuroscience

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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.

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Section: Resultsmentioning

confidence: 99%

Meta‐analysis of the effects of anti‐migraine therapeutics in the rat trigeminovascular nociception model as a tool for design optimization

Dolgorukova

Protsenko

Isaeva

et al. 2023

Eur J of Neuroscience

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show abstract

“…In one study (Akerman and Romero-Reyes, 2019), the effects of the drugs on the evoked activity were reported in absolute values, and the authors kindly provided the data expressed as % changes from baseline as well as numbers of units with C-fibre inputs. Dolgorukova et al (2020) reported medians and interquartile ranges, and means with SDs were obtained from the authors. The corresponding authors of the remaining 4 studies did not respond to our data request.…”

Section: Resultsmentioning

confidence: 99%

“…The high heterogeneity in the data set can also be caused by extreme effect sizes, while the pooled effect estimate can be highly dependent on a single experiment. According to sensitivity analysis, 2/21 experiments from 2 studies (Dolgorukova et al, 2020; Sokolov et al, 2008) were influential outliers (Supp. 3, Figures 4-5).…”

Section: Resultsmentioning

confidence: 99%

“…According to sensitivity analysis, 2/21 experiments from 2 studies (Dolgorukova et al, 2020;Sokolov et al, 2008) were influential outliers (Supp. 3, Figures 4-5).…”

Section: Meta-analysismentioning

confidence: 99%

“…The results before and after the removal of the influential outliers are presented in Table 4. The removed influential outliers were metoclopramide tested in Dolgorukova et al (2020), and valproate tested in Sokolov et al (2008). CI, confidence interval, MD, mean difference between treatment and control in %change of neuronal activity from baseline, PI, prediction interval.…”

Section: Meta-analysismentioning

confidence: 99%

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Meta-analysis of the effects of clinically-effective therapeutics in the preclinical migraine model as a tool for design optimisation

Dolgorukova

Protsenko

Isaeva

et al. 2022

Preprint

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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.

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Menthol dural application alters meningeal arteries tone and enhances excitability of trigeminocervical neurons in rats

Sokolov,

Mengal,

Berkovich

2024

Brain Research

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The Influence of Metoclopramide on Trigeminovascular Nociception: Possible Anti-migraine Mechanism of Action

Cited by 8 publications

References 80 publications

Meta‐analysis of the effects of anti‐migraine therapeutics in the rat trigeminovascular nociception model as a tool for design optimization

Meta‐analysis of the effects of anti‐migraine therapeutics in the rat trigeminovascular nociception model as a tool for design optimization

Meta-analysis of the effects of clinically-effective therapeutics in the preclinical migraine model as a tool for design optimisation

Menthol dural application alters meningeal arteries tone and enhances excitability of trigeminocervical neurons in rats

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