Division of Comparative Medicine, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Translational Research in Pain Program, North Carolina State University, Raleigh, North Carolina, United States of America.
PLoS One. 2022 Nov 21;17(11):e0277943. doi: 10.1371/journal.pone.0277943. eCollection 2022.
Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.
相对较少的工作评估了骨关节炎（OA）疾病和临床相关的疼痛结果在不同的 OA 大鼠模型中的测量。本研究的目的是比较化学和手术性 OA 模型在大鼠中的敏感性、疼痛和组织学疾病严重程度。通过关节内注射单碘乙酸（MIA）或前交叉韧带横断术和/或内侧半月板不稳定（ACL+DMM 或单独 DMM）诱导大鼠膝关节 OA。随着时间的推移，测量反射性（例如机械和热刺激）敏感性测量和非反射性测定（例如跛行、静态后肢负重不对称、动态步态分析）的疼痛。组织学评估关节退化。OA 诱导后 6 周，ACL+DMM 动物的视觉观察到的跛行明显大于 MIA 动物；然而，ACL+DMM 和 MIA 动物在行走和站立时的肢体使用中表现出相同的疼痛。与 ACL+DMM 动物相比，MIA 动物的热敏感性增加，但机械敏感性没有增加。在 6 周时，MIA 模型中的关节退化明显更严重。我们的初步数据表明，ACL+DMM 和 MIA 模型在临床相关的疼痛行为方面是相等的，但 MIA 模型随着时间的推移与更严重的组织学变化相关，可能使其更适合筛选疾病修饰剂。未来的工作应该根据复杂的疼痛行为以及对感觉系统和关节组织的生化、分子和影像学分析进一步描述每个模型，这将使模型选择和调查结果的决策更加明智。
