Prolonged Pain Research in Mice: Trends in Reference to the 3Rs

Balcombe, Jonathan; Ferdowsian, Hope; Briese, Lauren

doi:10.1080/10888705.2013.741004

Cited by 12 publications

(9 citation statements)

References 16 publications

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“…While the importance of preclinical evaluations in pain research is apparent [ 86 ], an important caveat in the use of the unanesthetized animal to study persistent, inescapable pain states is the need to minimize unnecessary stress and utilize sufficiently powered paradigms to minimize animal use [ 98 , 99 ]. Importantly, the models listed in Table 1 have been subject to approval in the US by the relevant institutional animal care and use committees.…”

Section: Preclinical Characterization Of the “Analgesic” Actions Of Amentioning

confidence: 99%

The search for novel analgesics: targets and mechanisms

et al. 2015

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The management of the pain state is of great therapeutic relevance to virtually every medical specialty. Failure to manage its expression has deleterious consequence to the well-being of the organism. An understanding of the complex biology of the mechanisms underlying the processing of nociceptive information provides an important pathway towards development of novel and robust therapeutics. Importantly, preclinical models have been of considerable use in determining the linkage between mechanism and the associated behaviorally defined pain state. This review seeks to provide an overview of current thinking targeting pain biology, the use of preclinical models and the development of novel pain therapeutics. Issues pertinent to the strengths and weaknesses of current development strategies for analgesics are considered.

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Section: Preclinical Characterization Of the “Analgesic” Actions Of Amentioning

confidence: 99%

The search for novel analgesics: targets and mechanisms

et al. 2015

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“…However, in our case, the number of time points is limited to at most 13 and cannot be increased dramatically for animal-ethical reasons. First, due to the three R principle [30,14], any animal experiment will only have a relatively small, limited number of observations. Second, we need some distinct distance between the developmental stages to detect a rise or a fall.…”

Section: Discussionmentioning

confidence: 99%

Change Point Detection For Clustered Expression Data In Short Time Series.

Sieg¹,

Sciesielski²,

Kirschner³

et al. 2021

Preprint

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Background: In longitudinal studies, observations are made over time. Hence, the single observations at each time point are dependent, making them a repeated measurement. In this work, we explore a different, counterintuitive setting: At each developmental time point, a lethal observation is performed on the pregnant or nursing mother. Therefore, the single time points are independent. Furthermore, the observation in the offspring at each time point is correlated with each other because each litter consists of several (genetically linked) littermates. In addition, the observed time series is short from a statistical perspective as animal ethics prevent killing more mother mice than absolutely necessary, and murine development is short anyway. We solve these challenges by using multiple contrast tests and visualizing the change point by the use of confidence intervals.Results: We used linear mixed models to model the variability of the mother. The estimates from the linear mixed model are then used in multiple contrast tests.There are a variety of contrasts and intuitively, we would use the Changepoint method. However, it does not deliver satisfying results. Interestingly, we found two other contrasts, both capable of answering different research questions in change point detection: i) Should a single point with change direction be found, or ii) Should the overall progression be determined? The Sequen contrast answers the first, the McDermott the second. Confidence intervals deliver effect estimates for the strength of the potential change point. Therefore, the scientist can define a biologically relevant limit of change depending on the research question.Conclusion: We present a solution with effect estimates for short independent time series with observations nested at a given time point. Multiple contrast tests produce confidence intervals, which allow determining the position of change points or to visualize the expression course over time. We suggest to use McDermott’s method to determine if there is an overall significant change within the time frame, while Sequen is better in determining specific change points. In addition, we offer a short formula for the estimation of the maximal length of the time series.

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“…Rather, these terms would have been included and addressed in the IACUC-approved protocols associated with the work represented in the 55 publications (uncited). The second parameter featured was an elevation in pain research using animal models over recent decades (Balcombe et al, 2013). Since the authors focused on models of chronic pain from 2000 to 2010, such an observation is to be expected.…”

Section: Reductionmentioning

confidence: 98%

“…A recent publication (Balcombe et al, 2013) claimed that pain research in general fails to consider the 3Rs, with a primary emphasis on a perceived lack of attention to the Reduction arm. However, the premise upon which this was based was seriously flawed.…”

Section: Reductionmentioning

confidence: 98%