Volume 1, Issue 2, May 2017, Page: 24-33
Symptomatic Disc Herniations: A Review to Understand Pathophysiology and Prediction of Outcomes
Tagbo Ilozue, Department of Neurosurgery, Royal Victoria Infirmary, Newcastle, UK
Mohamed Abdelsadg, Department of Neurosurgery, Ninewells Hospital, Dundee, UK
Avinash Kumar Kanodia, Department of Radiology, Ninewells Hospital, Dundee, UK
Kismet Hossain-Ibrahim, Department of Neurosurgery, Ninewells Hospital, Dundee, UK
Received: Feb. 28, 2017;       Accepted: Mar. 24, 2017;       Published: Apr. 10, 2017
DOI: 10.11648/j.cnn.20170102.11      View  1468      Downloads  111
Abstract
Lumbar disc herniation is a common condition with a significant impact on health and economics worldwide. Although deemed unrequired in the majority of cases; surgery has a cardinal role in the management of this disease. Most patients will experience symptomatic improvement following conservative treatment, in fact some will experience complete recovery of their symptoms. Nonetheless the mechanism behind this spontaneous improvement is currently poorly understood, yet it offers the potential to inform therapeutic options that might promote more rapid recovery and prevent the establishment of long-term complications. This review summarises the available literature on the pathophysiological events occurring following lumbar disc herniation, with some relevant reflections on the clinical picture. Also the review highlights the current gaps in our knowledge, and stresses some of the debatable concepts in managing the disease, in order to identify areas where future research might help explain the process of spontaneous recovery from symptomatic lumbar disc herniations and also suggest direction of further research to have a positive impact about outcomes.
Keywords
Lumbar Disc Herniation, Disc Prolapse, Pathophysiology, Radiculopathy
To cite this article
Tagbo Ilozue, Mohamed Abdelsadg, Avinash Kumar Kanodia, Kismet Hossain-Ibrahim, Symptomatic Disc Herniations: A Review to Understand Pathophysiology and Prediction of Outcomes, Clinical Neurology and Neuroscience. Vol. 1, No. 2, 2017, pp. 24-33. doi: 10.11648/j.cnn.20170102.11
Copyright
Copyright © 2017 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Fardon DF, Milette PC. Nomenclature and classification of lumbar disc pathology: recommendations of the combined task forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology. Spine 2001; 26: E93–E113.
[2]
Milette PC. Classification, diagnostic imaging, and imaging characterization of a lumbar herniated disk. Radiol Clin North Am 2000; 38: 1267–1292.
[3]
Mixter WJ, Barr JS. Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med 1934; 211: 210–225.
[4]
Cheung KMC, Karppinen J, Chan D, Ho DWH, Song Y-Q, Sham P, et al. Prevalence and pattern of lumbar magnetic resonance imaging changes in a population study of one thousand forty-three individuals. Spine 2009; 34: 934–940.
[5]
Boos N, Semmer N, Elfering A, Schade V, Gal I, Zanetti M, et al. Natural history of individuals with asymptomatic disc abnormalities in magnetic resonance imaging: predictors of low back pain-related medical consultation and work incapacity. Spine 2000; 25: 1484–1492.
[6]
Battié MC, Videman T, Parent E. Lumbar disc degeneration: epidemiology and genetic influences. Spine 2004; 29: 2679–2690.
[7]
Koes BW, van Tulder MW, Peul WC. Diagnosis and treatment of sciatica. BMJ 2007; 334: 1313–1317.
[8]
Valat J-P, Genevay S, Marty M, Rozenberg S, Koes B. Sciatica. Best Pract Res Clin Rheumatol 2010; 24: 241–252.
[9]
Fairbank JC. Sciatica: An archaic term. BMJ 2007; 335: 112.
[10]
Konstantinou K, Dunn KM. Sciatica: review of epidemiological studies and prevalence estimates. Spine 2008; 33: 2464–2472.
[11]
Frymoyer JW. Back pain and sciatica. N Engl J Med 1988; 318: 291–300.
[12]
Jacobs WCH, van Tulder M, Arts M, Rubinstein SM, van Middelkoop M, Ostelo R, et al. Surgery versus conservative management of sciatica due to a lumbar herniated disc: a systematic review. Eur Spine J 2011; 20: 513–522, 2011.
[13]
Koes BW, van Tulder M, Lin C-WC, Macedo LG, McAuley J, Maher C. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J 2010; 19: 2075–2094.
[14]
Benson RT, Tavares SP, Robertson SC, Sharp R, Marshall RW. Conservatively treated massive prolapsed discs: a 7-year follow-up. Ann R Coll Surg Engl 2010; 92: 147–153.
[15]
Benoist M. The natural history of lumbar disc herniation and radiculopathy. Joint Bone Spine 2002; 69: 155–160.
[16]
Barzouhi el A, Vleggeert-Lankamp CLAM, Lycklama à Nijeholt GJ, Van der Kallen BF, van den Hout WB, Jacobs WCH, et al. Magnetic resonance imaging in follow-up assessment of sciatica. N Engl J Med 2013; 368: 999–1007.
[17]
Yoshida M, Nakamura T, Sei A, Kikuchi T, Takagi K, Matsukawa A. Intervertebral disc cells produce tumor necrosis factor α, interleukin-1β, and monocyte chemoattractant protein-1 immediately after herniation: an experimental study using a new hernia model. Spine 2005; 30: 55–61.
[18]
Lindblom K, Hultqvist G. Absorption of protruded disc tissue. J Bone Joint Surg Am 1950; 32: 557–560.
[19]
Teplick JG, Haskin ME. Spontaneous regression of herniated nucleus pulposus. AJR Am J Roentgenol 1985; 145: 371–375.
[20]
Saal JAJ, Saal JSJ, Herzog RJR. The natural history of lumbar intervertebral disc extrusions treated nonoperatively. Spine 1990; 15: 683–686.
[21]
Ikeda T, Nakamura T, Kikuchi T, Umeda S, Senda H, Takagi K. Pathomechanism of spontaneous regression of the herniated lumbar disc: histologic and immunohistochemical study. Journal of Spinal Disorders & Techniques 1996; 9: 136–140.
[22]
Doita M, Kanatani T, Harada T, Mizuno K. Immunohistologic study of the ruptured intervertebral disc of the lumbar spine. Spine 1996; 21: 235–241.
[23]
Tsuru M, Nagata K, Ueno T, Jimi A, Irie K, Yamada A, et al. Electron microscopic observation of established chondrocytes derived from human intervertebral disc hernia (KTN-1) and role of macrophages in spontaneous regression of degenerated tissues. The Spine Journal 2001; 1: 422–431.
[24]
Takada T, Nishida K, Doita M, Kurosaka M. Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc. Spine 2002; 27: 1526–1530.
[25]
Grönblad M, Habtemariam A, Virri J, Seitsalo S, Vanharanta H, Guyer RD. Complement membrane attack complexes in pathologic disc tissues. Spine 2003; 28: 114–118.
[26]
Geiss A, Larsson K, Rydevik B, Takahashi I, Olmarker K. Autoimmune properties of nucleus pulposus: an experimental study in pigs. Spine 2007; 32: 168–173.
[27]
Minamide A, Hashizume H, Yoshida M, Kawakami M, Hayashi N, Tamaki T. Effects of basic fibroblast growth factor on spontaneous resorption of herniated intervertebral discs: an experimental study in the rabbit. Spine 1999; 24: 940.
[28]
Kawaguchi S, Yamashita T, Yokogushi K, Murakami T, Ohwada O, Sato N. Immunophenotypic analysis of the inflammatory infiltrates in herniated intervertebral discs. Spine 2001; 26: 1209–1214.
[29]
Fadda A, Oevermann A, Vandevelde M, Doherr MG, Forterre F, Henke D. Clinical and pathological analysis of epidural inflammation in intervertebral disk extrusion in dogs. J Vet Intern Med 2013; 27: 924–934.
[30]
Minamide A, Tamaki T, Hashizume H, Yoshida M, Kawakami M, Hayashi N. Effects of steroid and lipopolysaccharide on spontaneous resorption of herniated intervertebral discs: an experimental study in the rabbit. Spine 1998; 23: 870–876.
[31]
Autio RA, Karppinen J, Niinimäki J, Ojala R, Kurunlahti M, Haapea M, et al. Determinants of spontaneous resorption of intervertebral disc herniations. Spine 2006; 31: 1247–1252.
[32]
Komori H, Shinomiya K, Nakai O, Yamaura I, Takeda S, Furuya K. The natural history of herniated nucleus pulposus with radiculopathy. Spine 1996; 21: 225–229.
[33]
Virri J, Grönblad M, Seitsalo S, Habtemariam A, Kääpä E, Karaharju E. Comparison of the prevalence of inflammatory cells in subtypes of disc herniations and associations with straight leg raising. Spine 2001; 26: 2311–2315.
[34]
Grönblad M, Virri J, Seitsalo S, Habtemariam A, Karaharju E. Inflammatory cells, motor weakness, and straight leg raising in transligamentous disc herniations. Spine 2000; 25: 2803–2807.
[35]
Woertgen C, Rothoerl RD, Brawanski A. Influence of macrophage infiltration of herniated lumbar disc tissue on outcome after lumbar disc surgery. Spine 2000; 25: 871–875.
[36]
Doita M, Kanatani T, Ozaki T, Matsui N, Kurosaka M, Yoshiya S. Influence of macrophage infiltration of herniated disc tissue on the production of matrix metalloproteinases leading to disc resorption. Spine 2001; 26: 1522–1527.
[37]
Kang JD, Georgescu HI, McIntyre-Larkin L, Stefanovic-Racic M, Donaldson WF III, Evans CH. Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine 1996; 21: 271–277.
[38]
Goupille P, Jayson MI, Valat J-P, Freemont AJ Matrix metalloproteinases: the clue to intervertebral disc degeneration? Spine 1998; 23: 1612–1626.
[39]
Haro H, Komori H, Kato T, Hara Y, Tagawa M, Shinomiya K, et al. Experimental studies on the effects of recombinant human matrix metalloproteinases on herniated disc tissues--how to facilitate the natural resorption process of herniated discs. J Orthop Res 2005; 23: 412–419.
[40]
Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol 2013; 229: 176–185.
[41]
Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol 2005; 6: 1191–1197.
[42]
Habtemariam A, Grönblad M, Virri J, Karaharju E. A comparative immunohistochemical study of inflammatory cells in acute-stage and chronic-stage disc herniations. Spine 1998; 23: 2159–2165.
[43]
Kikuchi T, Nakamura T, Ikeda T, Ogata H, Takagi K. Monocyte chemoattractant protein-1 in the intervertebral disc. A histologic experimental model. Spine 1998; 23: 1091–1099.
[44]
Sonnemann KJK, Bement WMW: Wound repair. toward understanding and integration of single-cell and multicellular wound responses. Annu Rev Cell Dev Biol 2011; 27: 237–263.
[45]
Rothoerl RD, Woertgen C, Brawanski A. Pain resolution after lumbar disc surgery is influenced by macrophage tissue infiltration. A prospective consecutive study on 177 patients. Journal of Clinical Neuroscience 2002; 9: 633–636.
[46]
Peul WC, van Houwelingen HC, van den Hout WB, Brand R, Eekhof JAH, Tans JTJ, et al. Surgery versus prolonged conservative treatment for sciatica. N Engl J Med 2007; 356: 2245–2256.
[47]
Mulleman D, Mammou S, Griffoul I, Watier H, Goupille P. Pathophysiology of disk-related sciatica. I.-Evidence supporting a chemical component. Joint Bone Spine 2006; 73: 151–158.
[48]
Byun WM, Ahn SH, Ahn MW. Value of 3D MR lumbosacral radiculography in the diagnosis of symptomatic chemical radiculitis. American Journal of Neuroradiology 2012; 33: 529–534.
[49]
Jensen MC, Brant-Zawadzki MN, Obuchowski N, Modic MT, Malkasian D, Ross JS. Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med 1994; 331: 69–73.
[50]
van Rijn JC, Klemetso N, Reitsma JB, Majoie CBLM, Hulsmans FJ, Peul WC, et al. Symptomatic and asymptomatic abnormalities in patients with lumbosacral radicular syndrome: Clinical examination compared with MRI. Clinical Neurology and Neurosurgery 2006; 108: 553–557.
[51]
Zou J, Yang H, Miyazaki M, Wei F, Hong SW, Yoon SH, et al. Missed lumbar disc herniations diagnosed with kinetic magnetic resonance imaging. Spine 2008; 33: E140–E144.
[52]
Tarantino UU, Fanucci EE, Iundusi RR, Celi MM, Altobelli SS, Gasbarra EE, et al. Lumbar spine MRI in upright position for diagnosing acute and chronic low back pain: statistical analysis of morphological changes. J Orthop Traumatol 2013; 14: 15–22.
[53]
Gibson JNA, Waddell G. Surgical interventions for lumbar disc prolapse: updated Cochrane Review. Spine 2007; 32: 1735–1747.
[54]
Prasad KSM, Gregson BA, Hargreaves G, Byrnes T, Winburn P, Mendelow AD. Inversion therapy in patients with pure single level lumbar discogenic disease: a pilot randomized trial. Disabil Rehabil 2012; 34: 1473–1480.
[55]
Yabuki S, Onda A, Kikuchi S, Myers RR. Prevention of compartment syndrome in dorsal root ganglia caused by exposure to nucleus pulposus. Spine 2001; 26: 870–875.
[56]
Olmarker K, Blomquist J, Strömberg J, Nannmark U, Thomsen P, Rydevik B. Inflammatogenic properties of nucleus pulposus. Spine 1995; 20: 665–669.
[57]
Katsuno R, Hasegawa T, Iwashina T, Sakai D, Mikawa Y, Mochida J. Age-related effects of cocultured rat nucleus pulposus cells and macrophages on nitric oxide production and cytokine imbalance. Spine 2008; 33: 845–849.
[58]
Takada T, Nishida K, Maeno K, Kakutani K, Yurube T, Doita M, et al. Intervertebral disc and macrophage interaction induces mechanical hyperalgesia and cytokine production in a herniated disc model in rats. Arthritis & Rheumatism 2012; 64: 2601–2610.
[59]
Murata Y, Onda A, Rydevik B, Takahashi I, Takahashi K, Olmarker K. Changes in pain behavior and histologic changes caused by application of tumor necrosis factor-alpha to the dorsal root ganglion in rats. Spine 2006; 31: 530–535.
[60]
Takahashi H, Suguro T, Okazima Y, Motegi M, Okada Y, Kakiuchi T. Inflammatory cytokines in the herniated disc of the lumbar spine. Spine 1996; 21: 218–224.
[61]
Genevay S, Finckh A, Payer M, Mezin F, Tessitore E, Gabay C, et al. Elevated levels of tumor necrosis factor-alpha in periradicular fat tissue in patients with radiculopathy from herniated disc. Spine 2008; 33: 2041–2046.
[62]
Andrade P, Hoogland G, Garcia MA, Steinbusch HW, Daemen MA, Visser-Vandewalle V. Elevated IL-1β and IL-6 levels in lumbar herniated discs in patients with sciatic pain. Eur Spine J 2013; 22: 714–720.
[63]
Peng B, Wu W, Li Z, Guo J, Wang X. Chemical radiculitis. Pain 2007; 127: 11–16.
[64]
Schäfers M, Sorkin LS, Geis C, Shubayev VI. Spinal nerve ligation induces transient upregulation of tumor necrosis factor receptors 1 and 2 in injured and adjacent uninjured dorsal root ganglia in the rat. Neuroscience Letters 2003; 347: 179–182.
[65]
Jensen TS, Albert HB, Sorensen JS, Manniche C, Leboeuf-Yde C. Magnetic resonance imaging findings as predictors of clinical outcome in patients with sciatica receiving active conservative treatment. Journal of manipulative and physiological therapeutics 2007; 30: 98–108.
[66]
Adams MA, Stefanakis M, Dolan P: Healing of a painful intervertebral disc should not be confused with reversing disc degeneration: implications for physical therapies for discogenic back pain. Clin Biomech (Bristol, Avon) 2010; 25: 961–971.
[67]
Hampton D, Laros G, McCarron R, Franks D. Healing potential of the anulus fibrosus. Spine 1989; 14: 398–401.
[68]
Osti OL, Vernon-Roberts B, Fraser RD. 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. Spine 1990; 15: 762–767.
[69]
Coventry MB, Ghormley RK, Kernohan JW. The Intervertebral Disc: Its microscopic Anatomy and Pathology Part II. Changes in the Intervertebral Disc Concomitant with Age. J Bone Joint Surg Am 1945; 27: 233–247.
[70]
Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y. The pathogenesis of discogenic low back pain. J Bone Joint Surg Br 2005; 87: 62–67.
[71]
Ahn S-H, Cho Y-W, Ahn M-W, Jang S-H, Sohn Y-K, Kim H-S. mRNA expression of cytokines and chemokines in herniated lumbar intervertebral discs. Spine 2002; 27: 911–917.
[72]
Martin P. Wound healing-aiming for perfect skin regeneration. Science 1997; 276: 75–81.
[73]
Peng B, Hao J, Hou S, Wu W, Jiang D, Fu X, et al. Possible pathogenesis of painful intervertebral disc degeneration. Spine 2006; 31: 560–566.
[74]
Gruber HE, Fisher EC Jr, Desai B, Stasky AA, Hoelscher G, Hanley EN Jr. Human intervertebral disc cells from the annulus: three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. Exp Cell Res 1997; 235: 13.
[75]
Buckley CD, Gilroy DW, Serhan CN, Stockinger B, Tak PP. The resolution of inflammation. Nat Rev Immunol 2013; 13: 59–66.
[76]
Andrade P, Visser-Vandewalle V, Philippens M, Daemen MA, Steinbusch HWM, Buurman WA, et al. Tumor necrosis factor-α levels correlate with postoperative pain severity in lumbar disc hernia patients: opposite clinical effects between tumor necrosis factor receptor 1 and 2. Pain 2011; 152: 2645–2652.
[77]
Autio RA, Karppinen J, Kurunlahti M, Kyllönen E, Vanharanta H, Tervonen O. Gadolinium diethylenetriaminepentaacetic acid enhancement in magnetic resonance imaging in relation to symptoms and signs among sciatic patients: a cross-sectional study. Spine 2002; 27: 1433–1437.
[78]
Rothoerl RD, Woertgen C, Holzschuh M, Rueschoff J, Brawanski A. Is there a clinical correlate to the histologic evidence of inflammation in herniated lumbar disc tissue? Spine 1998; 23: 1197–1200.
[79]
Alini M, Eisenstein SM, Ito K, Little C, Kettler AA, Masuda K, et al. Are animal models useful for studying human disc disorders/degeneration? Eur Spine J 2008; 17: 2–19.
[80]
Ohtori S, Miyagi M, Eguchi Y, Inoue G, Orita S, Ochiai N, et al. Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: a prospective randomized study. Spine 2012; 37: 439–444.
[81]
Korhonen T, Karppinen J, Paimela L, Malmivaara A, Lindgren K-A, Bowman C, et al. The treatment of disc-herniation-induced sciatica with infliximab: one-year follow-up results of FIRST II, a randomized controlled trial. Spine 2006; 31: 2759–2766.
[82]
Olmarker K, Byrod G, Cornefjord M, Nordborg C, Rydevik B. Effects of methylprednisolone on nucleus pulposus- induced nerve root injury. Spine 1994; 19: 1803–1808.
[83]
Jones KG, Barnett HC. The use of hydrocortisone in spinalsurgery. South Med J 1955; 48: 617–623.
[84]
King JS. Dexamethasone—a helpful adjunct in management after lumbar discectomy. Neurosurgery 1984; 14: 697–700.
[85]
Naylor A, Flowers MW, Bramley JE. The value of dexamethasone in the postoperative treatment of lumbar disc prolapse. Orthop Clin North Am 1977; 8: 3–8.
[86]
Watters WC III, Temple AP, Granberry M. The use of dexamethasone in primary lumbar disc surgery. A prospective, randomized, double-blind study. Spine 1989; 14: 440–442.
[87]
Lowell, Troy D., Thomas J. Errico, and Mark S. Eskenazi. "Use of epidural steroids after discectomy may predispose to infection." Spine 2000; 25 (4): 516-519.
[88]
Yang, Scott, et al. Preoperative epidural injections are associated with increased risk of infection after single-level lumbar decompression. The Spine Journal 2016; 16. 2: 191-196.
[89]
Ranguis SC, Li D, Webster AC. Perioperative epidural steroids for lumbar spine surgery in degenerative spinal disease: a review. Journal of Neurosurgery: Spine 2010; 13 (6): 745-757.
[90]
Jamjoom BA, Jamjoom AB. Efficacy of intraoperative epidural steroids in lumbar discectomy: a systematic review. BMC Musculoskeletal Disorders 2014; 15 (1): 146.
[91]
Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine 2006; 31: 2151–2161.
[92]
Lotz JC, Ulrich JA. Innervation, inflammation, and hypermobility may characterize pathologic disc degeneration: review of animal model data. J Bone Joint Surg Am 2006; 88: 76–82.
[93]
Nerlich AG, Schaaf R, Wälchli B, Boos N. Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs. Eur Spine J 2007; 16: 547–555.
[94]
Urban JPG, Smith S, Fairbank JCT. Nutrition of the intervertebral disc. Spine 2004; 29: 2700–2709.
[95]
Kobayashi S, Meir A, Kokubo Y, Uchida K, Takeno K, Miyazaki T, et al. Ultrastructural analysis on lumbar disc herniation using surgical specimens: role of neovascularization and macrophages in hernias. Spine 2009; 34: 655–662.
[96]
Roy S, Sen CK. miRNA in wound inflammation and angiogenesis. Microcirculation 2012; 19: 224–232.
[97]
Ulrich JA, Liebenberg EC, Thuillier DU, Lotz JC. ISSLS prize winner: repeated disc injury causes persistent inflammation. Spine 2007; 32: 2812–2819.
[98]
Zhou G, Dai L, Jiang X, Ma Z, Ping J, Li J, et al. Effects of human midkine on spontaneous resorption of herniated intervertebral discs. International Orthopaedics (SICOT) 2010; 34: 103–108.
[99]
Dahm KT, Brurberg KG, Jamtvedt G, Hagen KB. Advice to rest in bed versus advice to stay active for acute low-back pain and sciatica. Cochrane Database Syst Rev 2010; CD007612–CD007612.
[100]
Malmivaara A, Häkkinen U, Aro T, Heinrichs M-L, Koskenniemi L, Kuosma E, et al. The treatment of acute low back pain—bed rest, exercises, or ordinary activity? N Engl J Med 1995; 332: 351–355.
[101]
Stirling A, Worthington T, Rafiq M, Lambert PA, Elliott TS. Association between sciatica and Propionibacterium acnes. Lancet 2001; 357: 2024–2025, 2001.
[102]
Agarwal VJ, Golish R, Kondrashov D, Alamin TF. Results of Bacterial Culture from Surgically Excised Intervertebral Disc in 52 Patients Undergoing Primary Lumbar Microdiscectomy at a Single Level. The Spine Journal 2010; 10: S45–S46, 2010.
[103]
Albert HB, Sorensen JS, Christensen BS, Manniche C. Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy. Eur Spine J 2013; 22: 697–707.
[104]
Battié MC, Videman T. Lumbar disc degeneration: epidemiology and genetics. J Bone Joint Surg Am 2006; 88 Suppl 2: 3–9.
[105]
Paesold G, Nerlich AG, Boos N. Biological treatment strategies for disc degeneration: potentials and shortcomings. Eur Spine J 2007; 16: 447–468.
[106]
Takahashi M, Haro H, Wakabayashi Y, Kawa-Uchi T, Komori H, Shinomiya K. The association of degeneration of the intervertebral disc with 5a/6a polymorphism in the promoter of the human matrix metalloproteinase-3 gene. Journal of Bone & Joint Surgery, British Volume 2001; 83: 491–495.
[107]
Seki S, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, et al. A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease. Nat Genet 2005; 37: 607–612.
[108]
Solovieva S, Leino-Arjas P, Saarela J, Luoma K, Raininko R, Riihimäki H. Possible association of interleukin 1 gene locus polymorphisms with low back pain. Pain 2004; 109: 8–19.
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