Wawrose Richard A, Couch Brandon K, Dombrowski Malcom, Chen Stephen R, Oyekan Anthony, Dong Qing, Wang Dong, Zhou Chaoming, Chen Joseph, Modali Karthik, Johnson Marit, Sedor-Schiffhauer Zachary, Hitchens T Kevin, Jin Tao, Bell Kevin M, Lee Joon Y, Sowa Gwendolyn A, Vo Nam V
Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery University of Pittsburgh Pittsburgh Pennsylvania USA.
Animal Imaging Center University of Pittsburgh Pittsburgh Pennsylvania USA.
JOR Spine. 2022 May 13;5(2):e1202. doi: 10.1002/jsp2.1202. eCollection 2022 Jun.
Previous animal models of intervertebral disc degeneration (IDD) rely on open surgical approaches, which confound the degenerative response and pain behaviors due to injury to surrounding tissues during the surgical approach. To overcome these challenges, we developed a minimally invasive percutaneous puncture procedure to induce IDD in a rat model.
Ten Fischer 344 male rats underwent percutaneous annular puncture of lumbar intervertebral discs (IVDs) at L2-3, L3-4, and L4-5. Ten unpunctured rats were used as controls. Magnetic resonance imagings (MRIs), serum biomarkers, and behavioral tests were performed at baseline and 6, 12, and 18 weeks post puncture. Rats were sacrificed at 18 weeks and disc histology, immunohistochemistry, and glycosaminoglycan (GAG) assays were performed.
Punctured IVDs exhibited significant reductions in MRI signal intensity and disc volume. Disc histology, immunohistochemistry, and GAG assay results were consistent with features of IDD. IVD-punctured rats demonstrated significant changes in pain-related behaviors, including total distance moved, twitching frequency, and rearing duration.
This is the first reported study of the successful establishment of a reproducible rodent model of a percutaneous lumbar annular puncture resulting in discogenic pain. This model will be useful to test therapeutics and elucidate the basic mechanisms of IDD and discogenic pain.
以往的椎间盘退变(IDD)动物模型依赖开放手术方法,这会因手术过程中对周围组织的损伤而混淆退变反应和疼痛行为。为克服这些挑战,我们开发了一种微创经皮穿刺程序,以在大鼠模型中诱导椎间盘退变。
10只Fischer 344雄性大鼠在L2 - 3、L3 - 4和L4 - 5节段接受腰椎间盘(IVD)的经皮环形穿刺。10只未穿刺的大鼠用作对照。在基线以及穿刺后6、12和18周进行磁共振成像(MRI)、血清生物标志物检测和行为测试。在18周时处死大鼠,并进行椎间盘组织学、免疫组织化学和糖胺聚糖(GAG)检测。
穿刺后的IVD在MRI信号强度和椎间盘体积上显著降低。椎间盘组织学、免疫组织化学和GAG检测结果与IDD特征一致。IVD穿刺大鼠在疼痛相关行为上表现出显著变化,包括总移动距离、抽搐频率和站立持续时间。
这是首次报道成功建立一种可重复的经皮腰椎环形穿刺导致盘源性疼痛的啮齿动物模型的研究。该模型将有助于测试治疗方法,并阐明IDD和盘源性疼痛的基本机制。