Voluntary intake of paracetamol-enriched drinking water and its influence on the success of embryo transfer in mice

Fleischmann, Thea; Arras, Margarete; Sauer, Mareike; Saleh, Lanja; Rülicke, Thomas; Jirkof, Paulin

doi:10.1016/j.rvsc.2016.12.005

Cited by 10 publications

(9 citation statements)

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“…NaCl n = 18, Cer n = 17, Cer + Bup n = 16, Cer + PT n = 15, Cer + Met n = 16. (Fleischmann et al, 2017). Although we saw some animals with a calculated intake of analgesia higher than the sought dosage per 24 h, we did not observe any signs of overdosing, which was in line with our previous work (unpublished data).…”

Section: Discussionsupporting

confidence: 92%

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

Durst

Graf

et al. 2021

Front. Physiol.

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Pancreatitis is known to be painful in humans and companion animals. However, the extent of pain in experimental mouse models of acute pancreatitis is unknown. Consequently, the severity classification of acute pancreatitis in mice is controversially discussed and standardized pain management is missing. In this study, we investigated acute Cerulein-induced pancreatitis with pain-specific and well-being orientated parameters to detect its impact on mice. Male C57BL/6J male mice were injected with Cerulein; animals that received saline injections served as control group. The animals were observed for weight change and water intake. To assess pain, behaviors like stretch-and-press and reduced rearing, the Mouse Grimace Scale, and von Frey hypersensitivity were assessed. Fecal corticosterone metabolites and burrowing behavior were assessed to detect changes in the animal’s well-being. Pancreatitis severity was evaluated with amylase and lipase in the blood and pancreas histology. To investigate whether different analgesics can alleviate signs of pain, and if they influence pancreas inflammation, animals received Buprenorphine, Paracetamol in combination with Tramadol, or Metamizole in the drinking water. The calculated intake of these analgesics via drinking reached values stated to be efficient for pain alleviation. While pancreatitis did not seem to be painful, we detected acute pain from Cerulein injections that could not be alleviated by analgesics. The number of inflammatory cells in the pancreas did not differ with the analgesic administered. In conclusion: (1) Cerulein injections appear to be acutely painful but pain could not be alleviated by the tested analgesics, (2) acute pancreatitis induced by our protocol did not induce obvious signs of pain, (3) analgesic substances had no detectable influence on inflammation. Nevertheless, protocols inducing more severe or even chronic pancreatitis might evoke more pain and analgesic treatment might become imperative. Considering our results, we recommend the use of Buprenorphine via drinking water in these protocols. Further studies to search for efficient analgesics that can alleviate the acute pain induced by Cerulein injections are needed.

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Section: Discussionsupporting

confidence: 92%

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

Durst

Graf

et al. 2021

Front. Physiol.

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“…We therefore assume that spillage was not a major issue in our study and that some animals indeed had a high water, and therefore Paracetamol, intake 55 . This variability of (medicated) water intake has been reported and can be considered a disadvantage of administering analgesia in the drinking water 56 , 57 . In our study, the Paracetamol intake was not confirmed by analysis of blood concentration.…”

Section: Discussionmentioning

confidence: 93%

Lidocaine and bupivacaine as part of multimodal pain management in a C57BL/6J laparotomy mouse model

Durst

Arras

Palme

et al. 2021

Sci Rep

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While the use of local anesthesia as part of multimodal pain management is common practice in human and veterinarian surgery, these drugs are not applied routinely in rodent surgery. Several recommendations on the use of local anesthesia exist, but systematic studies on their efficacy and side effects are lacking. In the present study, male and female C57BL/6J mice were subjected to a sham vasectomy or a sham embryo transfer, respectively. We tested whether a mixture of subcutaneously injected Lidocaine and Bupivacaine in combination with systemic Paracetamol applied via drinking water results in superior pain relief when compared to treatment with local anesthesia or Paracetamol alone. We applied a combination of methods to assess behavioral, emotional, and physiological changes indicative of pain. Voluntary Paracetamol intake via drinking water reached the target dosage of 200 mg/kg in most animals. Local anesthesia did not lead to obvious side effects such as irregular wound healing or systemic disorders. No relevant sex differences were detected in our study. Sevoflurane anesthesia and surgery affected physiological and behavioral measurements. Surprisingly, Paracetamol treatment alone significantly increased the Mouse Grimace Scale. Taken together, mice treated with a combination of local anesthesia and systemic analgesia did not show fewer signs of post-surgical pain or improved recovery compared to animals treated with either local anesthesia or Paracetamol.

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“…Furthermore, the ability to produce a pregnancy after ET has been reported as possible to be achieved with less than five embryos [ 2 ], 8 to 12 embryos [ 1 ] or less than 15 embryos [ 4 ] through unilateral transfer. Additionally, the analgesic and anesthetic protocol must be considered as a potential source of variation although several options are described as having no significant effect on the ET outcome [ 19 , 20 , 21 , 22 , 23 ], such as carprofen, used for this experimental work.…”

Section: Introductionmentioning

confidence: 99%

C57BL/6J and B6129F1 Embryo Transfer: Unilateral and Bilateral Transfer, Embryo Number and Recipient Female Background Control for the Optimization of Embryo Survival and Litter Size

Lamas¹,

Franquinho²,

Morgado³

et al. 2020

Animals

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Embryo transfer (ET) is a common procedure in rodent facilities. Optimizing this technique may help to reduce the number of animals, but little information is available regarding wild type strains and the conditions that affect embryo transfer. To explore this theme, 2-cell C57BL/6J embryos were transferred after overnight culture of freshly collected zygotes using different conditions: unilateral transfers using a total of 6, 8, 12, 15, 20 and 25 embryos were performed initially; then, this strain was also used for bilateral transfers using a total of 6, 12 and 20 embryos equally divided by the two oviducts. Groups of 25 embryos were not tested for the bilateral technique, since this condition produced the lower success rate when using the unilateral technique and 20 embryos would still represent a large number of embryos. A group of 2-cell B6129F1 embryos was also transferred using unilateral and bilateral ET with 6, 12 and 20 embryos. Crl:CD1(ICR) were used as recipient females for non-reciprocal transfers and C57BL/6J were used to test reciprocal transfers (only tested for six C57BL/6J unilateral transfers). Unilateral transfers using C57BL/6J mice produced higher success rates using six embryos, compared to the other groups transferred unilaterally (p-values between 0.0001 and 0.0267), but the mean number of pups per litter was not different among groups. Bilateral transfer produced higher number of pups when 20 embryos were divided by the two oviducts compared to six (p = 0.0012) or 12 (p = 0.0148) embryos, but with no differences in success rates. No statistical differences were found between the groups of B6129F1, but better results were obtained on bilateral transfers using a total of six embryos. For the strain tested (C57BL/6J), the uterine environment (Crl:CD1(ICR) or C57BL/6J recipient) does not impact the outcome of the technique. These results complement previous work published using genetically engineered mice strains and show that unilateral transfers using low number of embryos (6), produce better outcomes when compared to bilateral or unilateral transfers using more embryos. It also highlights differences between the outcome of bilateral transfers in the two strains tested. A set of historical data of genetically engineered mice at a C57BL/6J background was also included, confirming that lower embryo numbers are related to higher success rates. Together, the outcome of these experiments can be important to reduce the number of recipient and donor females, optimize embryo transfers and improve animal welfare discouraging the use of a more invasive technique.

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Voluntary intake of paracetamol-enriched drinking water and its influence on the success of embryo transfer in mice

Cited by 10 publications

References 32 publications

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

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

Lidocaine and bupivacaine as part of multimodal pain management in a C57BL/6J laparotomy mouse model

C57BL/6J and B6129F1 Embryo Transfer: Unilateral and Bilateral Transfer, Embryo Number and Recipient Female Background Control for the Optimization of Embryo Survival and Litter Size

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