Analysis of Pain and Analgesia Protocols in Acute Cerulein-Induced Pancreatitis in Male C57BL/6 Mice

Durst, Mattea; Graf, Theresia Reding; Graf, Rolf; Kron, Mareike; Arras, Margarete; Zechner, Dietmar; Palme, Rüpert; Talbot, Steven R.; Jirkof, Paulin

doi:10.3389/fphys.2021.744638

Cited by 7 publications

(9 citation statements)

References 44 publications

(68 reference statements)

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“…That this animal model is quite severe is also supported by the low survival rate ranging from 64-70 % [66–68]. In contrast, the survival rates of pancreatitis at 99 % [61], the CCl 4 model at 100 % [69], and the PDA model at 83 % [70] were reported to be higher.…”

Section: Discussionmentioning

confidence: 88%

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Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases

Talbot

Kumstel

Schulz

et al. 2022

Preprint

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The fundament of an evidence-based severity assessment in laboratory animal science is reliable distress parameters. Many readouts are used to evaluate and determine animal distress and the severity of experimental procedures. Therefore, we analyzed four distinct parameters like the body weight, burrowing behavior, nesting, and distress score in the four gastrointestinal animal models (pancreatic ductal adenocarcinoma (PDA), pancreatitis, CCl4intoxication, and bile duct ligation (BDL)). Further, we determined the parameters‘ robustness in various experimental subgroups due to slight variations like drug treatment or telemeter implantations. We used non-parametric bootstrapping to get robust estimates and 95 % confidence intervals for the experimental groups. It was found that the performance of the readout parameters is model-dependent and that the distress score is prone to experimental variation. On the other hand, we also found that burrowing and nesting can be more robust than, e.g., the body weight when evaluating PDA. However, the body weight still was highly robust in BDL, pancreatitis, and CCl4intoxication. To address the complex nature of the multi-dimensional severity space, we used the Relative Severity Assessment (RELSA) procedure to combine multiple distress parameters into a score and mapped the subgroups and models against a defined reference set obtained by telemeter implantation. This approach allowed us to compare the severity of individual animals in the experimental subgroups using the maximum achieved severity (RELSAmax). With this, the following order of severity was found for the animal models: CCl4< PDA ≈ Pancreatitis < BDL. Furthermore, the robustness of the RELSA procedure and outcome was externally validated with a reference set from another laboratory also obtained from telemeter implantation. Since the RELSA procedure reflects the multi-dimensional severity information and is highly robust in estimating the quantitative severitywithinandbetweenmodels, it can be deemed a valuable tool for laboratory animal severity assessment.

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Section: Discussionmentioning

confidence: 88%

“…In contrast, the survival rates of pancreatitis at 99 % [61], the CCl 4 model at 100 % [69], and the PDA model at 83 % [70] were reported to be higher. Suppose one considers the implantation of a transmitter as a surgical intervention, which causes moderate distress as suggested by the EU-Commission Guideline in Annex XIII [11].…”

Section: Discussionmentioning

confidence: 90%

Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases

Talbot

Kumstel

Schulz

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…That this animal model is quite severe is also supported by the low survival rate ranging from 64 to 70% 67 – 69 . In contrast, the survival rates of pancreatitis at 99% 61 , the CCl 4 model at 100% 70 , and the PDA model at 83% 71 were reported to be higher.…”

Section: Discussionmentioning

confidence: 90%

“…Indeed, both behavior tests have been reported to detect stress and suffering in many distinct animal models. For example, in animal models for colitis 59 , Parkinson disease 60 , pancreatitis 61 , epilepsy 62 , 63 , and depression 64 . However, a robust increase in the distress score could only be detected in the BDL animal model.…”

Section: Discussionmentioning

confidence: 99%

Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases

Talbot

Kumstel

Schulz

et al. 2023

Sci Rep

Self Cite

View full text Add to dashboard Cite

The fundament of an evidence-based severity assessment in laboratory animal science is reliable distress parameters. Many readouts are used to evaluate and determine animal distress and the severity of experimental procedures. Therefore, we analyzed four distinct parameters like the body weight, burrowing behavior, nesting, and distress score in the four gastrointestinal animal models (pancreatic ductal adenocarcinoma (PDA), pancreatitis, CCl4 intoxication, and bile duct ligation (BDL)). Further, we determined the parameters’ robustness in various experimental subgroups due to slight variations like drug treatment or telemeter implantations. We used non-parametric bootstrapping to get robust estimates and 95% confidence intervals for the experimental groups. It was found that the performance of the readout parameters is model-dependent and that the distress score is prone to experimental variation. On the other hand, we also found that burrowing and nesting can be more robust than, e.g., the body weight when evaluating PDA. However, the body weight still was highly robust in BDL, pancreatitis, and CCl4 intoxication. To address the complex nature of the multi-dimensional severity space, we used the Relative Severity Assessment (RELSA) procedure to combine multiple distress parameters into a score and mapped the subgroups and models against a defined reference set obtained by telemeter implantation. This approach allowed us to compare the severity of individual animals in the experimental subgroups using the maximum achieved severity (RELSAmax). With this, the following order of severity was found for the animal models: CCl4 < PDA ≈ Pancreatitis < BDL. Furthermore, the robustness of the RELSA procedure and outcome was externally validated with a reference set from another laboratory also obtained from telemeter implantation. Since the RELSA procedure reflects the multi-dimensional severity information and is highly robust in estimating the quantitative severity within and between models, it can be deemed a valuable tool for laboratory animal severity assessment.

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“…One of the most important symptoms and diagnostic criteria for AP is intensive abdominal pain which is present in more than 95% of the patients 3,34 . Generally, pain is associated with anxiety-like behaviour, and open led tests could reveal this association 35,36 . As DMTS has analgesic effects, 20 the nociception and the behaviour of the animals were tested in AP after DMTS treatment.…”

Section: Discussionmentioning

confidence: 99%

The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis

Orján

Kormányos

Für

et al. 2022

Preprint

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Several organosulfur compounds, such as dimethyl trisulfide (DMTS), exhibit anti-inflammatory properties. Our aims were to investigate the effects of DMTS on acute pancreatitis (AP) and its mechanism of action in both in vivo and in vitro studies. AP was induced in FVB/n mice or Wistar rats by caerulein or L-ornithine-HCl, respectively. DMTS treatments were applied subcutaneously. AP severity was evaluated with histological scoring of the pancreas, pancreatic water content and myeloperoxidase activity measurements. The behaviour of animals were followed. Western blot was performed to determine the extent of pancreatic heat shock protein 72 (HSP72) expression. In vitro acinar viability, reactive oxygen species (ROS) production, and intracellular Ca2+ concentrations were determined in isolated pancreatic acinar cells. DMTS dose dependently reduced the severity of AP. It decreased the pancreatic infiltration of leukocytes, myeloperoxidase activity and cellular damage in mice, but it was less effective in rats. During AP, DMTS upregulated the HSP72 expression. DMTS showed cytoprotection against H2O2 and AP inducing agents, it reduced the level of ROS, and altered the caerulein-evoked Ca2+ signals. Overall, DMTS significantly ameliorated the severity of AP and protected pancreatic acinar cells. Our results suggest that DMTS have anti-inflammatory effects, so organosulfur compounds are worth further investigation in this potentially lethal disease.

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Analysis of Pain and Analgesia Protocols in Acute Cerulein-Induced Pancreatitis in Male C57BL/6 Mice

Cited by 7 publications

References 44 publications

Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases

Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases

Robustness of a multivariate composite score when evaluating distress of animal models for gastrointestinal diseases

The anti-inflammatory effect of dimethyl trisulfide in experimental acute pancreatitis

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