Abstract

Simple SummaryPain management during in vivo experiments can considerably improve the wellbeing of animals. However, often it is not clear, which drugs are best for the animals and how to apply these drugs without causing stress. In this study, we evaluated mice when metamizole or tramadol was provided via drinking water. Neither of these two drugs reduced the amount of consumed water or body weight in healthy mice or influenced their natural behavior, such as nest building or burrowing activity. Both analgesics were then given to mice suffering from chronic pancreatitis. Mice drinking tramadol supplemented water, at some time-points, experienced less loss in body weight and consumed more water than mice drinking metamizole. However, no major differences in other methods measuring wellbeing of mice was observed. In conclusion, both analgesics can be used during chronic pancreatitis, but tramadol seems to be moderately advantageous when compared to metamizole.Pain management during in vivo experiments is an animal welfare concern and is in many countries also legally required. In this study, we evaluated C57Bl/6J mice when 3 g/L metamizole or 1 g/L tramadol was provided via drinking water, before and during cerulein-induced chronic pancreatitis. Supplementation of drinking water with metamizole or tramadol did not significantly reduce the amount of consumed water. In order to evaluate the wellbeing of mice, a distress score, burrowing activity, nesting behavior, and body weight was assessed. Before induction of pancreatitis, neither tramadol nor metamizole influenced these readout parameters. Chronic pancreatitis caused a significantly increased distress score, decreased burrowing activity and a reduction in body weight. Mice drinking tramadol-supplemented water experienced less loss in body weight and consumed more water than mice drinking metamizole, at a few time-points during chronic pancreatitis. Pancreatic atrophy, a characteristic feature of chronic pancreatitis was not differentially influenced by either analgesic. In conclusion, both analgesics can be used during 33 days of chronic pancreatitis, but tramadol seems to be moderately advantageous when compared to metamizole.

Highlights

  • Analgesia during potentially painful in vivo experiments is ethically required and in many countries legally obligatory as well [1,2,3]

  • Before evaluating metamizole and tramadol during chronic pancreatitis, we verified that these analgesics did not influence our readout parameters for animal distress

  • We tested in the pre-experimental phase, if these analgesics did influence the distress score, burrowing activity, nesting behavior or the body weight

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Summary

Introduction

Analgesia during potentially painful in vivo experiments is ethically required and in many countries legally obligatory as well [1,2,3]. Optimizing pain treatment for specific animal models. Animals 2020, 10, 2306 will improve the well-being of animals and will thereby provide the basis for future research on pathophysiological processes and in vivo evaluation of drugs. When deciding for appropriate analgesia, one problematic issue is the possible interference of analgesic treatment, with the studied pathology. It is important to assess that analgesia does not interfere with the pathophysiology of a studied disease. Since it was demonstrated that metamizole does not interfere with progression of cerulein-induced acute pancreatitis in mice [5], some studies use metamizole as an analgesic when studying this disease in preclinical studies [6]. Metamizole is often chosen to treat human pancreatitis patients [7,8], but other analgesics, such as tramadol are used [9,10]

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