Drug Discovery and Biomedical Sciences, Medical University of South Carolina.
Department of Biomedical Science, The University of Alabama at Birmingham.
J Vis Exp. 2024 Aug 2(210). doi: 10.3791/66053.
The purpose of this protocol is to guide researchers in performing a palpation-guided technique of intra-articular knee injection in guinea pigs and assessment using micro-computed tomography. Dunkin-Hartley guinea pigs are robust models for osteoarthritis research as they spontaneously develop osteoarthritis in their knees. Intra-articular drug delivery is a common method to study the effects of an investigational drug in vivo. In humans, therapeutic agents administered via intra-articular injection can offer pain relief and delay further progression of osteoarthritis. As with any species, the introduction of a needle into a joint space has the potential to cause injury, which can result in pain, lameness, or infection. Such adverse events can compromise animal welfare, confound study results, and necessitate additional animals to achieve study objectives. As such, it is imperative to develop proper injection techniques to prevent complications, especially in longitudinal studies that require multiple, repeated intra-articular injections. Using the presented methodology, five guinea pigs received bilateral knee injections under general anesthesia. Seven days after injection, animals were humanely euthanized for analysis of osteoarthritis severity. No adverse events occurred following anesthesia or knee injections, including limping, pain, or infection. X-ray micro-computed tomography analysis of the knee can detect pathologic changes associated with osteoarthritis. Micro-computed tomography data indicates osteoarthritis is more severe in older animals, as indicated by increased bone mineral density and trabecular thickness with age. These results are consistent with histologic changes and Modified Mankin scores, an established and widely used scoring system to assess arthritis severity in these same animals. This protocol can be utilized to refine intra-articular injections in guinea pigs.
本方案旨在指导研究人员对豚鼠进行触诊引导式关节内膝关节注射,并使用微计算机断层扫描进行评估。Dunkin-Hartley 豚鼠是骨关节炎研究的强大模型,因为它们的膝关节会自发地发生骨关节炎。关节内药物输送是一种常见的方法,可在体内研究研究药物的作用。在人类中,通过关节内注射给予的治疗剂可以提供疼痛缓解并延缓骨关节炎的进一步进展。与任何物种一样,将针引入关节空间都有可能造成损伤,从而导致疼痛、跛行或感染。这些不良事件会损害动物福利、混淆研究结果,并需要额外的动物来实现研究目标。因此,必须开发适当的注射技术以预防并发症,特别是在需要多次重复关节内注射的纵向研究中。使用本方案,五只豚鼠在全身麻醉下接受双侧膝关节注射。注射后 7 天,对动物进行安乐死以分析骨关节炎严重程度。麻醉或膝关节注射后均未发生不良事件,包括跛行、疼痛或感染。膝关节的 X 射线微计算机断层扫描分析可以检测与骨关节炎相关的病理变化。微计算机断层扫描数据表明,随着年龄的增长,关节炎更为严重,表现为骨矿物质密度和小梁厚度增加。这些结果与组织学变化和改良 Mankin 评分一致,改良 Mankin 评分是一种广泛使用的评估这些相同动物关节炎严重程度的评分系统。本方案可用于改进豚鼠的关节内注射。