Effects of Untreated Pain, Anesthesia, and Analgesia in Animal Experimentation

Jirkof, Paulin; Potschka, Heidrun

doi:10.1007/978-3-030-66147-2_5

Cited by 4 publications

(10 citation statements)

References 128 publications

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“…The reliable and robust monitoring and scoring of pain in laboratory rodents is an important basis for optimized perisurgical pain management, which always needs to be adjusted to the animal characteristics and the specific intervention. Moreover, for the selection of the analgetic regimen, a potential impact on scientific readout parameters needs to be considered ( 5 ). Considering the multitude of influencing factors, it is obvious that there are no universally valid analgetic concepts applicable to all experimental interventions.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, it should be considered that different degrees of uncontrolled pain contribute to the variance of data obtained in animal models, thereby increasing the number of animals needed. Resultantly, uncontrolled or insufficiently controlled pain can significantly affect various readout parameters and can therefore restrict study quality (3)(4)(5). In this context, manifold effects need to be considered when including effects on the neuroendocrine, immune, cardiovascular, respiratory, autonomous, and central nervous systems.…”

Section: Introductionmentioning

confidence: 99%

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Grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats—A systematic review

et al. 2022

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Several studies suggested an informative value of behavioral and grimace scale parameters for the detection of pain. However, the robustness and reliability of the parameters as well as the current extent of implementation are still largely unknown. In this study, we aimed to systematically analyze the current evidence-base of grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats. The following platforms were searched for relevant articles: PubMed, Embase via Ovid, and Web of Science. Only full peer-reviewed studies that describe the grimace scale, burrowing, and/or nest building as pain parameters in the post-surgical phase in mice and/or rats were included. Information about the study design, animal characteristics, intervention characteristics, and outcome measures was extracted from identified publications. In total, 74 papers were included in this review. The majority of studies have been conducted in young adult C57BL/6J mice and Sprague Dawley and Wistar rats. While there is an apparent lack of information about young animals, some studies that analyzed the grimace scale in aged rats were identified. The majority of studies focused on laparotomy-associated pain. Only limited information is available about other types of surgical interventions. While an impact of surgery and an influence of analgesia were rather consistently reported in studies focusing on grimace scales, the number of studies that assessed respective effects was rather low for nest building and burrowing. Moreover, controversial findings were evident for the impact of analgesics on post-surgical nest building activity. Regarding analgesia, a monotherapeutic approach was identified in the vast majority of studies with non-steroidal anti-inflammatory (NSAID) drugs and opioids being most commonly used. In conclusion, most evidence exists for grimace scales, which were more frequently used to assess post-surgical pain in rodents than the other behavioral parameters. However, our findings also point to relevant knowledge gaps concerning the post-surgical application in different strains, age levels, and following different surgical procedures. Future efforts are also necessary to directly compare the sensitivity and robustness of different readout parameters applied for the assessment of nest building and burrowing activities.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats—A systematic review

et al. 2022

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“…This study was carried out for 14 days and the rabbits were observed for food and water intake, body weight, the sign of illness, any kind of seeable skin irritation/toxicity, and mortality. A possible source of suffering in animal research is pain induced by experimental procedures, injuries, and diseases [ 48 ]. To alleviate the stress/suffering of rabbits, a parenteral anesthetic combination like ketamine and xylazine have become the agents of choice for rabbit anesthesia due to their efficacy, low cost, and ease of administration [ 49 ].…”

Section: Methodsmentioning

confidence: 99%

Developed meloxicam loaded microparticles for colon targeted delivery: Statistical optimization, physicochemical characterization, and in-vivo toxicity study

et al. 2022

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The study aimed to fabricate and evaluate Meloxicam (MLX) loaded Hydroxypropyl Methylcellulose (HPMC) microparticles for colon targeting because MLX is a potent analgesic used in the treatment of pain and inflammation associated with colorectal cancer (CRC). Nevertheless, its efficiency is limited by poor solubility and gastrointestinal tracts (GIT) associated side effects. Seventeen formulations of MLX loaded HPMC microparticles were fabricated by the oil-in-oil (O/O)/ emulsion solvent evaporation (ESE) technique. A 3-factor, 3-level Box Behnken (BBD) statistical design was used to estimate the combined effects of the independent variables on the dependent variables (responses), such as the percent yield (R1), the entrapment efficiency (EE) (R2), mean particle size (R3) and in vitro percentage of cumulative drug release (R4). For physicochemical characterization FTIR, XRD, DSC, and SEM analyses were performed. Biocompatibility and non-toxicity were confirmed by in-vivo acute oral toxicity determination. The percentage yield and EE were 65.75–90.71%, and 70.62–88.37%, respectively. However, the mean particle size was 62.89–284.55 μm, and the in vitro cumulative drug release percentage was 74.25–92.64% for 24 hours. FTIR analysis showed that the composition of the particles was completely compatible, while XRD analysis confirmed the crystalline nature of the pure drug and its transition into an amorphous state after formulation. DSC analysis revealed the thermal stability of the formulations. The SEM analysis showed dense spherical particles. The toxicity study in albino rabbits showed no toxicity and was found biocompatible. The histopathological evaluation showed no signs of altered patterns. Results of this study highlighted a standard colonic drug delivery system with the ability to improve patient adherence and reduce GIT drug-associated side effects in CRC treatment.

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“…Lack of analgesia and oligoanalgesia (failure to provide adequate analgesia in patients) remains a persistent problem in animal-based research ( Richardson and Flecknell, 2005 ; Stokes et al, 2009 ; Jirkof, 2017 ; Flecknell, 2018 ; Foley et al, 2019 ). While the type and severity of pain can be anticipated in the context of surgical interventions in experimental animals, scientists often refrain from the application of an adequate analgesia regimen because of concerns about an effect of analgesic drugs on readout parameters ( Jirkof, 2017 ; Peterson et al, 2017 ; Jirkof and Potschka, 2021 ). However, it needs to be considered that there is a multitude of analgesic compounds from different drug classes, providing the option to carefully choose the regimen based on the expected interfering effects ( Vadivelu et al, 2016 ; Jirkof, 2017 ; Jirkof and Potschka, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…While the type and severity of pain can be anticipated in the context of surgical interventions in experimental animals, scientists often refrain from the application of an adequate analgesia regimen because of concerns about an effect of analgesic drugs on readout parameters ( Jirkof, 2017 ; Peterson et al, 2017 ; Jirkof and Potschka, 2021 ). However, it needs to be considered that there is a multitude of analgesic compounds from different drug classes, providing the option to carefully choose the regimen based on the expected interfering effects ( Vadivelu et al, 2016 ; Jirkof, 2017 ; Jirkof and Potschka, 2021 ). Moreover, study design can be adjusted to prevent interference, for example with an extension of recovery phases or the inclusion of respective control groups ( Jirkof, 2017 ; Moser, 2020 ; Jirkof and Potschka, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Anesthesia and analgesia for experimental craniotomy in mice and rats: a systematic scoping review comparing the years 2009 and 2019

et al. 2023

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Experimental craniotomies are a common surgical procedure in neuroscience. Because inadequate analgesia appears to be a problem in animal-based research, we conducted this review and collected information on management of craniotomy-associated pain in laboratory mice and rats. A comprehensive search and screening resulted in the identification of 2235 studies, published in 2009 and 2019, describing craniotomy in mice and/or rats. While key features were extracted from all studies, detailed information was extracted from a random subset of 100 studies/year. Reporting of perioperative analgesia increased from 2009 to 2019. However, the majority of studies from both years did not report pharmacologic pain management. Moreover, reporting of multimodal treatments remained at a low level, and monotherapeutic approaches were more common. Among drug groups, reporting of pre- and postoperative administration of non-steroidal anti-inflammatory drugs, opioids, and local anesthetics in 2019 exceeded that of 2009. In summary, these results suggest that inadequate analgesia and oligoanalgesia are persistent issues associated with experimental intracranial surgery. This underscores the need for intensified training of those working with laboratory rodents subjected to craniotomies.Systematic review registrationhttps://osf.io/7d4qe.

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Effects of Untreated Pain, Anesthesia, and Analgesia in Animal Experimentation

Cited by 4 publications

References 128 publications

Grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats—A systematic review

Grimace scale, burrowing, and nest building for the assessment of post-surgical pain in mice and rats—A systematic review

Developed meloxicam loaded microparticles for colon targeted delivery: Statistical optimization, physicochemical characterization, and in-vivo toxicity study

Anesthesia and analgesia for experimental craniotomy in mice and rats: a systematic scoping review comparing the years 2009 and 2019

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