• Masayuki Miyagi, Tetsuhiro Ishikawa, Hiroto Kamoda, Miyako Suzuki, Kenichi Murakami, Masataka Shibayama, Sumihisa Orita, Yawara Eguchi, Gen Arai, Yoshihiro Sakuma, Gou Kubota, Yasuhiro Oikawa, Tomoyuki Ozawa, Yasuchika Aoki, Tomoaki Toyone, Kazuhisa Takahashi, Gen Inoue, Mamoru Kawakami, and Seiji Ohtori.
• Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. masayuki008@aol.com
• Spine. 2012 Oct 1;37(21):1810-8.

Study DesignAnimal model of intravertebral disc (IVD) degeneration.ObjectiveTo examine production of inflammatory mediators in IVDs and neuropeptides in dorsal root ganglia (DRGs) in rat models of IVD compression and injury.Summary Of Background DataSensory nerve fibers in IVDs and inflammatory mediator responses have been verified in animal models of IVD injury. However, the IVD injury in animals incompletely models degenerated human IVDs causing discogenic low back pain, because human IVDs are also subject to compression.MethodsExperimental groups (controls, IVD injury, IVD compression, and their combination) of Sprague Dawley rats were prepared. Fluoro-Gold (FG; Fluorochrome, Denver, CO) was applied into coccygeal IVDs. Inflammatory mediators in IVDs, including nerve growth factor, tumor necrosis factor α, interleukin 1β, and interleukin 6, were quantified using enzyme-linked immunosorbent assays. DRGs were immunostained for calcitonin gene-related peptide, activating transcription factor 3, and growth-associated phosphoprotein 43.ResultsThe upregulation of inflammatory mediators was transient in the IVD injury group but delayed and long-lasting in the IVD compression group. When the IVD injury and compression were combined, the upregulation of inflammatory mediators was long-lasting through 8 weeks. The proportion of calcitonin gene-related peptide-immunoreactive neurons among Fluoro-Gold-labeled neurons remained significantly higher in the IVD injury, compression, and combination groups than in the controls. In contrast, increases in the proportions of activating transcription factor 3-immunoreactive or growth-associated phosphoprotein 43-immunoreactive neurons in the IVD injury group animals were transient but long-lasting in the compression and combination groups compared with controls.ConclusionDisc injury in rats produces persistent increases in neuropeptides in DRGs but only transient increases in inflammatory mediators in IVDs. On the contrary, disc compression in rats produces a long-lasting increase in inflammatory mediators in IVDs and neuropeptides in DRGs. Moreover, disc compression induces persistent nerve injury and regeneration of the afferent fibers innervating IVDs.

55 keywords...

hide…