Evaluation of Analgesic Efficacy of Meloxicam and 2 Formulations of Buprenorphine after Laparotomy in Female Sprague–Dawley Rats

Nunamaker, Elizabeth A.; Goldman, Julia; Adams, Cynthia R.; Fortman, Jeffrey D

doi:10.30802/aalas-jaalas-17-000129

Cited by 27 publications

(16 citation statements)

References 24 publications

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“…40 Although meloxicam has been administered at a dose of 20 mg/kg in other stocks and strains of mice, the current study is the first published report of C57BL/6 mice that received meloxicam once daily at this dose and for this duration. Whether the injection-site pathology that we noted in the current study is related to the strain, meloxicam brand, volume administered, number of doses administered in the same location, 26 or another variable is unknown. However, the injection volume is unlikely to have contributed to pathology, because our maximal volume of 0.5 mL SC is much less than the 2 to 3 mL frequently recommended, 34 and rats have displayed similar pathology after receiving much smaller volume of 5 mg/ mL meloxicam (0.04−0.08 mL).…”

Section: Discussionmentioning

confidence: 97%

“…Ulcerative dermatitis has been reported after 3 once-daily subcutaneous doses of either 1 or 2 mg/kg of rats. 26 This study 26 and the current study used the same brand of meloxicam, which is formulated at a concentration of 5 mg/mL. Another similarity between the two studies is the daily repetition of injections: the rats received 3 daily injec-tions, whereas the mice in the current study received 6.…”

Section: Discussionmentioning

confidence: 97%

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Concentration-dependent Toxicity after Subcutaneous Administration of Meloxicam to C57BL/6N Mice (Mus musculus)

Sarfaty

Zeiss

Willis

et al. 2019

j am assoc lab anim sci

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Studies using the Mouse Grimace Scale have shown that for many NSAID, including meloxicam, minimal doses of at least 20 mg/kg may be necessary to achieve adequate peri- and post-operative analgesia in mice. However, more data are needed to determine whether such NSAID doses exceed the threshold for gastrointestinal ulceration or induce other relevant pathology. We administered equal volumes of saline or injectable meloxicam (1 or 5 mg/mL) at a dose of 20 mg/kg SC to 20 young adult male and female C57BL/6N mice daily for 6 d and performed necropsies on all mice on the seventh day. Mice given 5 mg/mL meloxicam subcutaneously developed significantly more severe pathology at the injection site than saline controls. Pathology was characterized by full-thickness epidermal necrosis; cavitary lesions within subcutis, muscle, or fat; steatitis; and myositis. Mice that received 1 mg/mL meloxicam subcutaneously developed lesions that were qualitatively similar but far less severe than those after 5 mg/mL. However, no pathologic lesions typically associated with NSAID toxicity, such as gastric ulceration and liver and kidney lesions, were seen. These results demonstrate that although meloxicam injected subcutaneously causes concentration-dependent skin pathology at the injection site, a dose of 20 mg/kg can be safely administered subcutaneously at a concentration of 1 mg/mL for as long as 6 d.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Concentration-dependent Toxicity after Subcutaneous Administration of Meloxicam to C57BL/6N Mice (Mus musculus)

Sarfaty

Zeiss

Willis

et al. 2019

j am assoc lab anim sci

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show abstract

“…29,30,32,34,129,131 While it can be used to specifically assess pain, 3,12,46,52,59,61,69,95,111,[124][125][126]128,130,145,147 reductions in burrowing activity can also identify the influence of a range of factors, not all of which may be associated with pain, such as cognitive dysfunction, anxiety, systemic bacterial and viral infections, and inflammation. 24,27,29,[31][32][33][34]47,55,57,98,144 As such, burrowing may be viewed as a surrogate measure of pain in rodents, and also as a reflection of instrumental activities of daily living (IADL), an outcome used in humans to reflect the impact of disabilities such as pain on day-to-day activities (for example, general mobility, care of others, maintaining the living space). 88 Factors other than pain that result in a reduction in burrowing behavior have been better characterized in mice and these include neurodegenerative disease, anxiety, and systemic infection or inflammation, thus interpretation of changes in burrowing behavior needs to be case-specific.…”

Section: Burrowing Behaviorsmentioning

confidence: 99%

“…A comparison between grimace scales and a standard/traditional assessment method has been evaluated with both the MGS and RGS. 26,68,98,134 In these cases, mechanical hypersensitivity testing with von Frey filaments has been performed with interesting results. With the MGS, in an inflammation model (zymosan injection into the hind paw or ankle joint), an analgesic effect of acetaminophen could be detected; however, the same dose of acetaminophen (300 mg/kg, SC) did not significantly reduce mechanical hypersensitivity.…”

Section: Physiologic Assessments Of Pain In Laboratory Mice and Ratsmentioning

confidence: 99%

A Review of Pain Assessment Methods in Laboratory Rodents

2019

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Ensuring that laboratory rodent pain is well managed underpins the ethical acceptability of working with these animals in research. Appropriate treatment of pain in laboratory rodents requires accurate assessments of the presence or absence of pain to the extent possible. This can be challenging some situations because laboratory rodents are prey species that may show subtle signs of pain. Although a number of standard algesiometry assays have been used to assess evoked pain responses in rodents for many decades, these methods likely represent an oversimplification of pain assessment and many require animal handling during testing, which can result in stress-induced analgesia. More recent pain assessment methods, such as the use of ethograms, facial grimace scoring, burrowing, and nest-building, focus on evaluating changes in spontaneous behaviors or activities of rodents in their home environments. Many of these assessment methods are time-consuming to conduct. While many of these newer tests show promise for providing a more accurate assessment of pain, most require more study to determine their reliability and sensitivity across a broad range of experimental conditions, as well as between species and strains of animals. Regular observation of laboratory rodents before and after painful procedures with consistent use of 2 or more assessment methods is likely to improve pain detection and lead to improved treatment and care—a primary goal for improving overall animal welfare.

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“…49,163 However, in rats, a 2 mg/kg SC dose reduced behavioral signs of pain in a laparotomy model. 160…”

Section: Nonsteroidal Antiinflammatory Drugs (Nsaid)mentioning

confidence: 99%

Clinical Management of Pain in Rodents

2019

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The use of effective regimens for mitigating pain remain underutilized in research rodents despite the general acceptance of both the ethical imperative and regulatory requirements intended to maximize animal welfare. Factors contributing to this gap between the need for and the actual use of analgesia include lack of sufficient evidence-based data on effective regimens, under-dosing due to labor required to dose analgesics at appropriate intervals, concerns that the use of analgesics may impact study outcomes, and beliefs that rodents recover quickly from invasive procedures and as such do not need analgesics. Fundamentally, any discussion of clinical management of pain in rodents must recognize that nociceptive pathways and pain signaling mechanisms are highly conserved across mammalian species, and that central processing of pain is largely equivalent in rodents and other larger research species such as dogs, cats, or primates. Other obstacles to effective pain management in rodents have been the lack of objective, science-driven data on pain assessment, and the availability of appropriate pharmacological tools for pain mitigation. To address this deficit, we have reviewed and summarized the available publications on pain management in rats, mice and guinea pigs. Different drug classes and specific pharmacokinetic profiles, recommended dosages, and routes of administration are discussed, and updated recommendations are provided. Nonpharmacologic tools for increasing the comfort and wellbeing of research animals are also discussed. The potential adverse effects of analgesics are also reviewed. While gaps still exist in our understanding of clinical pain management in rodents, effective pharmacologic and nonpharmacologic strategies are available that can and should be used to provide analgesia while minimizing adverse effects. The key to effective clinical management of pain is thoughtful planning that incorporates study needs and veterinary guidance, knowledge of the pharmacokinetics and mechanisms of action of drugs being considered, careful attention to individual differences, and establishing an institutional culture that commits to pain management for all species as a central component of animal welfare.

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Evaluation of Analgesic Efficacy of Meloxicam and 2 Formulations of Buprenorphine after Laparotomy in Female Sprague–Dawley Rats

Cited by 27 publications

References 24 publications

Concentration-dependent Toxicity after Subcutaneous Administration of Meloxicam to C57BL/6N Mice (Mus musculus)

Concentration-dependent Toxicity after Subcutaneous Administration of Meloxicam to C57BL/6N Mice (Mus musculus)

A Review of Pain Assessment Methods in Laboratory Rodents

Clinical Management of Pain in Rodents

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