Side effects of pain and analgesia in animal experimentation

Jirkof, Paulin

doi:10.1038/laban.1216

Cited by 90 publications

(100 citation statements)

References 61 publications

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“…A safe and effective analgesic plan is critical to relieve pain, suffering and distress. Untreated pain can affect the animals' biology and add variability to the experiment; however specific pain management procedures can also introduce variability, affecting experimental data [195,196]. Under-reporting of welfare management procedures can also contribute to the perpetuation of non-compliant methodologies and insufficient or inappropriate use of analgesia [196] or other welfare measures.…”

Section: Explanationmentioning

confidence: 99%

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

Sert

Ahluwalia

Alam³

et al. 2019

Preprint

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Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments.Despite widespread endorsement by the scientific community, the impact of the ARRIVE guidelines on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This Explanation and Elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2019, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature.As a new international working groupthe authors of this publication, we have revised the guidelines to update them and facilitate their uptake; the ARRIVE guidelines 2019 are published alongside this paper [13]. We have updated the recommendations in line with current best practice, reorganised the information and classified the items into two sets. The ARRIVE Essential 10 constitute the minimum reporting requirement and the Recommended Set provides further context to the study described. The two sets help authors, journal staff, editors and reviewers use the guidelines in practice, and allow a pragmatic implementation with an initial focus on the most critical issues. Once the Essential 10 are consistently reported in manuscripts, items from the Recommended Set can be added to journal requirements over time until all 21 items are routinely reported in all manuscripts. Full methodology for the revision and the allocation of items into sets is described in the accompanying publication [13].A key aspect of the revision was to develop this Explanation and Elaboration document to provide background and rationale for each of the 21 items of ARRIVE 2019. Here we present additional guidance for each item and subitem, explain the importance of reporting this information in manuscripts that describe animal research, elaborate on what to report, and provide supporting evidence. Each subitem is also illustrated with examples of good reporting from the published literature. Box 1: GlossaryBias: Introduction of a systematic error in the estimated effect of an intervention, caused by inadequacies in the design, conduct, or analysis of an experiment.Effect size: Quantitative measure that estimates the magnitude of differences between groups, or relationships between variables. Experimental unit:Biological entity subjected to an intervention independently of all other units, such that it is possible to assign any two experimental units to different t...

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Section: Explanationmentioning

confidence: 99%

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

Sert

Ahluwalia

Alam³

et al. 2019

Preprint

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“…Reported side effects of NSAIDs are due mostly to their inhibition of COX-1 enzymes and include gastrointestinal ulceration, platelet inhibition, and renal toxicity [76]. MEL, however, preferentially inhibits the COX-2 enzymes which are associated with pain and inflammation.…”

Section: Lethality Associated With Vaccination and Analgesic Treatmentmentioning

confidence: 99%

The Use of Analgesics during Vaccination with a Live Attenuated Yersinia pestis Vaccine Alters the Resulting Immune Response in Mice

et al. 2019

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The administration of antipyretic analgesics prior to, in conjunction with, or due to sequelae associated with vaccination is a common yet somewhat controversial practice. In the context of human vaccination, it is unclear if even short-term analgesic regimens can significantly alter the resulting immune response, as literature exists to support several scenarios including substantial immune interference. In this report, we used a live attenuated Yersinia pestis vaccine to examine the impact of analgesic administration on the immune response elicited by a single dose of a live bacterial vaccine in mice. Mice were assessed by evaluating natural and provoked behavior, as well as food and water consumption. The resulting immune responses were assessed by determining antibody titers against multiple antigens and assaying cellular responses in stimulated splenocytes collected from vaccinated animals. We observed no substantial benefit to the mice associated with the analgesic administration. Splenocytes from both C57BL/6 and BALB/c vaccinated mice receiving acetaminophen have a significantly reduced interferon-gamma (IFN-γ) recall response. Additionally, there is a significantly lower immunoglobulin (Ig)G2a/IgG1 ratio in vaccinated BALB/c mice treated with either acetaminophen or meloxicam and a significantly lower IgG2c/IgG1 ratio in vaccinated C57BL/6 mice treated with acetaminophen. Taken together, our data indicate that the use of analgesics, while possibly ethically warranted, may hinder the accurate characterization and evaluation of novel vaccine strategies with little to no appreciable benefits to the vaccinated mice.

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“…Similarly, the complexities of human diagnoses are ignored or glossed over at our peril 17,48,49,54,55 . A recurrent theme of this paper, and this special issue, is that the role that good animal wellbeing plays in good science also cannot be ignored 26,[41][42][43][56][57][58] . Furthermore, factors that are controlled or standardized have also been widely shown to affect both the model and scientific outcomes, from the infectious agents we choose to exclude 59 , to the choice of bedding materials [60][61][62] and enrichment [63][64][65] , to cage changing practices 66 , to handling technique 58 , to the identity 31 or sex 67 of the experimenter.…”

Section: Six Questions: What Do We Choose To Ignore?mentioning

confidence: 99%

“…17,18,26-28,39,41) do not represent a voice in the wilderness, but one voice in a chorus and that this emerging literature 1,2,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]42,43 reflects a nascent discipline which can be codified as the study of how knowledge is gained from animal research. We propose the title "Therioepistemology" This focus issue of Lab Animal coincides with a tipping point in biomedical research.…”

mentioning

confidence: 99%

Introducing Therioepistemology: the study of how knowledge is gained from animal research

et al. 2017

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We are honored to write the opening article of this focus issue of Lab Animal. This focus issue could not occur at a more important time for biomedical research and the use of animals in science in general. The progressive worsening of success rates in human trials (currently 1 in 9 drugs entering human trials will succeed) 1-4 , combined with the explosion of interest in the reproducibility crisis 5-8 and the recognition that most drugs fail in human trials due to insufficient efficacy 1,2,4 , has led to a growing suspicion that the failure of translation from animal work to human outcomes may in some way reflect issues in animal research itself 5-19 -after all, every drug that fails in humans "worked" in an animal model. Indeed pharmaceutical companies continue to disinvest in internal animal R&D, a trend begun in the last decade, passing on the cost and risk to academia and startups 5,20 . Even this approach is not foolproof as pharmaceutical companies often cannot replicate the results of published work from academia 5,8,13 . Accordingly, there is a growing trend to focus on human, not animal, work for basic discovery 17 .Discarding animal research entirely is not the answer. When properly used, animal models have incredible value, not least the ability to follow biomarkers from birth to disease onset in a year or less (in the case of mice), which is impossible in humans 17,18 . There are patterns and principles that can help us identify models and results that are more or less likely to translate, and there are also easily realized, simple changes in the execution of animal work that will inherently improve translation [16][17][18] . This isn't a new concept; looking back over the last 10-15 years we can see many authors have been candid about the merits, strengths, weaknesses, reproducibility, and translatability of various animal models 1,2,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . Our goal with this article is to unite the common themes in this broader emerging literature and this special issue.Thus, the central point is that we (i.e., refs. 17,18,26-28,39,41) do not represent a voice in the wilderness, but one voice in a chorus and that this emerging literature 1,2,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]42,43 reflects a nascent discipline which can be codified as the study of how knowledge is gained from animal research. We propose the title "Therioepistemology" This focus issue of Lab Animal coincides with a tipping point in biomedical research. For the first time, the scale of the reproducibility and translatability crisis is widely understood beyond the small cadre of researchers who have been studying it and the pharmaceutical and biotech companies who have been living it. Here we argue that an emerging literature, including the papers in this focus issue, has begun to congeal around a set of recurring themes, which themselves represent a paradigm shift. This paradigm shift can be c...

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Side effects of pain and analgesia in animal experimentation

Cited by 90 publications

References 61 publications

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

The Use of Analgesics during Vaccination with a Live Attenuated Yersinia pestis Vaccine Alters the Resulting Immune Response in Mice

Introducing Therioepistemology: the study of how knowledge is gained from animal research

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