ISSLS prize winner: disc dynamic compression in rats produces long-lasting increases in inflammatory mediators in discs and induces long-lasting nerve injury and regeneration of the afferent fibers innervating discs: a pathomechanism for chronic discogenic low back pain

• Published in: Spine (Philadelphia, Pa. 1976) Vol. 37; no. 21; p. 1810
• Main Authors: Miyagi, Masayuki, Ishikawa, Tetsuhiro, Kamoda, Hiroto, Suzuki, Miyako, Murakami, Kenichi, Shibayama, Masataka, Orita, Sumihisa, Eguchi, Yawara, Arai, Gen, Sakuma, Yoshihiro, Kubota, Gou, Oikawa, Yasuhiro, Ozawa, Tomoyuki, Aoki, Yasuchika, Toyone, Tomoaki, Takahashi, Kazuhisa, Inoue, Gen, Kawakami, Mamoru, Ohtori, Seiji
• Format: Journal Article
• Language: English
• Published: United States 01.10.2012
• Subjects: Activating Transcription Factor 3 - metabolism; Animals; Awards and Prizes; Calcitonin Gene-Related Peptide - metabolism; Chronic Pain - etiology; Chronic Pain - metabolism; Chronic Pain - physiopathology; Enzyme-Linked Immunosorbent Assay; Ganglia, Spinal - metabolism; Ganglia, Spinal - pathology; Ganglia, Spinal - physiopathology; GAP-43 Protein - metabolism; Humans; Immunohistochemistry; Inflammation Mediators - metabolism; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Intervertebral Disc - innervation; Intervertebral Disc - metabolism; Intervertebral Disc - pathology; Intervertebral Disc Degeneration - complications; Intervertebral Disc Degeneration - metabolism; Intervertebral Disc Degeneration - physiopathology; Low Back Pain - etiology; Low Back Pain - metabolism; Low Back Pain - physiopathology; Male; Nerve Fibers - metabolism; Nerve Fibers - pathology; Nerve Regeneration; Neurons - metabolism; Neurons - pathology; Neurons, Afferent - metabolism; Neurons, Afferent - pathology; Neuropeptides - metabolism; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha - metabolism
• DOI: 10.1097/BRS.0b013e31824ffac6

Animal model of intravertebral disc (IVD) degeneration. To examine production of inflammatory mediators in IVDs and neuropeptides in dorsal root ganglia (DRGs) in rat models of IVD compression and injury. Sensory 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. Experimental 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. The 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. Disc 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.