Development of a novel model of intervertebral disc degeneration by the intradiscal application of monosodium iodoacetate (MIA) in rat

Abstract

BACKGROUND CONTEXT: Low back pain is one of the most common musculoskeletal disorders. Although, the pathology of intervertebral disc (IVD) degeneration has been modeled using various biological methods, these models are inadequate for simulating similar pathologic states in humans. PURPOSE: This study investigated whether monosodium iodoacetate (MIA) injection into the IVD of rats could generate a reliable model of IVD degeneration. STUDY DESIGN/SETTINGS: In vivo animal study. METHODS: MIA was injected into two-disc spaces (L4-5 and L5-6) of Sprague–Dawley rats. Their behaviors were examined by measuring weight load shifts from hind to forefoot, rearing, and von Frey tests. We examined the inhibition of pain behavior through intraperitoneal morphine injection and measured cyclooxygenase-2 (COX-2) and transcription factor nuclear factor-kappa B (NF-κB) levels in the IVD and dorsal root ganglion (DRG) by Western blot. Bone alterations were assessed by microfocus computed tomography (micro-CT), and IVD and/or cartilage changes were evaluated by hematoxylin and eosin and safranin-O staining and inducible nitric oxide synthase (iNOS) immunohistochemistry. The other authors declare no conflicts of interest. This project funded by the Memorial Fund and the National Research Foundation of Korea (NRF). RESULTS: We observed increased weight load shifts to the forefoot and decreased rearing. Morphine-injected rats showed reduced pain. NF-κB and COX-2 expression increased in the IVD and left and/or right DRG. Micro-CT analyses suggested progressive bone deformation. Histologic examination showed decreased IVD width and nucleus pulposus area. Cartilaginous changes indicated epiphyseal growth plate loss. Finally, iNOS expression was increased in the subchondral endplate. CONCLUSIONS: These results suggest that low back pain (LBP) models can be developed by MIA injection into the IVDs of rats and that an animal model is useful for exploring degenerative alterations in the affected discs. Therefore, MIA injection may be a useful model for the study of changes in the IVD to elucidate the mechanisms underlying clinical symptoms, such as LBP, in patients with IVD degeneration. CLINICAL SIGNIFICANCE: This model in which MIA was injected into the disc better represented the human histologic and behavioral characteristics than the existing puncture model. © 2021 Elsevier Inc.