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创伤性脑损伤后给予丁丙诺啡缓释LAB制剂的大鼠中与体重减轻相关的人道终点发生率增加:一项回顾性研究。

Increased incidence of weight-loss-associated humane endpoints in rats administered buprenorphine slow-release LAB formulation following traumatic brain injury: a retrospective study.

作者信息

Lilova Radina L, Hernandez Martina, Kelliher Corrina, Lafrenaye Audrey

机构信息

Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States.

Department of Neurology, Duke University School of Medicine, Durham, NC, United States.

出版信息

Front Neurol. 2024 Sep 23;15:1467419. doi: 10.3389/fneur.2024.1467419. eCollection 2024.

DOI:10.3389/fneur.2024.1467419
PMID:39376686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11456484/
Abstract

Traumatic brain injury (TBI) remains a significant global public health epidemic with adverse health and cost implications. Due to its complex, heterogeneous nature and wide-ranging impacts, definitive TBI treatments remain elusive. As such, continued laboratory research using animal models is warranted. In accordance with guidelines set forth for the humane treatment of research animals, TBI animal models are often administered analgesics for pain management. The choice of drug, timing, dose, and formulation of analgesic can vary depending on the study's unique needs and can potentially and unintentionally influence experimental results. In TBI studies utilizing rats as animal models, buprenorphine is a common analgesic administered. In addition to pain management in such studies, investigators must also monitor the research animals post-operatively and make the decision for humane euthanasia before intended experimental survival timepoint if the animals are assessed to be excessively suffering. This study investigated the differences in adult, male Sprague Dawley rats used for various TBI studies that reached weight-loss-induced humane endpoints following a single administration of buprenorphine slow-release LAB (bup-SR-LAB) or buprenorphine slow-release HCl (bup-SR-HCl). Our findings indicate that TBI-induced rats receiving bup-SR-LAB in conjunction with a secondary surgical insult such as artificial intracranial pressure elevation and/or osmotic pump implantation reach a weight-loss-induced humane euthanasia endpoint more often compared to sham-injured rats. When stratifying into the same groups, we did not find this pattern to hold true for rats administered bup-SR-HCl. Overall, this study contributes to the limited body of literature addressing different analgesic formulations' effects on laboratory animals.

摘要

创伤性脑损伤(TBI)仍然是一个严重的全球公共卫生问题,对健康和成本都有不利影响。由于其复杂、异质性的性质以及广泛的影响,确定的TBI治疗方法仍然难以捉摸。因此,有必要继续使用动物模型进行实验室研究。根据为研究动物的人道治疗制定的指导方针,TBI动物模型通常会使用镇痛药进行疼痛管理。药物的选择、给药时间、剂量和镇痛剂的配方可能会因研究的独特需求而有所不同,并可能无意中影响实验结果。在以大鼠为动物模型的TBI研究中,丁丙诺啡是一种常用的镇痛药。在这类研究中,除了进行疼痛管理外,研究人员还必须在术后监测实验动物,如果评估动物遭受过度痛苦,则要在预定的实验存活时间点之前做出人道安乐死的决定。本研究调查了在单次给予丁丙诺啡缓释LAB(bup-SR-LAB)或丁丙诺啡缓释HCl(bup-SR-HCl)后,用于各种TBI研究的成年雄性Sprague Dawley大鼠在达到因体重减轻而导致的人道终点方面的差异。我们的研究结果表明,与假手术损伤的大鼠相比,接受bup-SR-LAB并伴有继发性手术损伤(如人工颅内压升高和/或渗透压泵植入)的TBI诱导大鼠更常达到因体重减轻而导致的人道安乐死终点。当分为相同组时,我们发现给予bup-SR-HCl的大鼠不存在这种模式。总体而言,本研究为解决不同镇痛剂配方对实验动物影响的有限文献做出了贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df80/11456484/6b23b940d1dc/fneur-15-1467419-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df80/11456484/b9d4728e7970/fneur-15-1467419-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df80/11456484/f483d8b6eaaf/fneur-15-1467419-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df80/11456484/6b23b940d1dc/fneur-15-1467419-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df80/11456484/b9d4728e7970/fneur-15-1467419-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df80/11456484/f483d8b6eaaf/fneur-15-1467419-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df80/11456484/6b23b940d1dc/fneur-15-1467419-g003.jpg

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