• 1
    McCulloch JA. Focus issue on lumbar disc herniation: macro- and microdiscectomy. Spine 1996; 21: 4556S.
  • 2
    Ministry of Health, Labour and Welfare, Japan. Survey of Medical Care Activities in Public Health Insurance 2005. URL: In Japanese.
  • 3
    Hitselberger WE, Witten RM. Abnormal myelograms in asymptomatic patients. J Neurosurg 1968; 28: 2046.
  • 4
    Wiesel SW, Tsourmas N, Feffer HL, Citrin CM, Patronas N. A study of computer-assisted tomography. I. The incidence of positive CAT scans in an asymptomatic group of patients. Spine 1984; 9: 54951.
  • 5
    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: 6973.
  • 6
    Van der Windt DA, Simons E, Riphagen II, Ammendolia C, Verhagen AP, Laslett M, et al. Physical examination for lumbar radiculopathy due to disc herniation in patients with low-back pain. Cochrane Database Syst Rev 2010;( 2): CD007431.
  • 7
    Zwart JA, Sand T, Unsgaard G. Warm and cold sensory thresholds in patients with unilateral sciatica: C fibers are more severely affected than A-δ fibers. Acta Neurol Scand 1998; 97: 415.
  • 8
    Ahn SH, Cho YW, Ahn MW, Jang SH, Sohn YK, Kim HS. mRNA expression of cytokines and chemokines in herniated lumbar intervertebral discs. Spine 2002; 27: 9117.
  • 9
    Burke JG, Watson RW, Conhyea D, McCormack D, Dowling FE, Walsh MG, et al. Human nucleus pulposis can respond to a pro-inflammatory stimulus. Spine 2003; 28: 268593.
  • 10
    Burke JG, Watson RW, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM. Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J Bone Joint Surg Br 2002; 84: 196201.
  • 11
    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: 2717.
  • 12
    Kang JD, Georgescu HI, McIntyre-Larkin L, Stefanovic-Racic M, Evans CH. Herniated cervical intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine 1995; 20: 23738.
  • 13
    Li H, Zou X, Baatrup A, Lind M, Bunger C. Cytokine profiles in conditioned media from cultured human intervertebral disc tissue: implications of their effect on bone marrow stem cell metabolism. Acta Orthop 2005; 76: 11521.
  • 14
    Nygaard OP, Mellgren SI, Osterud B. The inflammatory properties of contained and noncontained lumbar disc herniation. Spine 1997; 22: 24848.
  • 15
    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: 21824.
  • 16
    Burke JG, Watson RW, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM. Spontaneous production of monocyte chemoattractant protein-1 and interleukin-8 by the human lumbar intervertebral disc. Spine 2002; 27: 14027.
  • 17
    O'Donnell JL, O'Donnell AL. Prostaglandin E2 content in herniated lumbar disc disease. Spine 1996; 21: 16535.
  • 18
    Willburger RE, Wittenberg RH. Prostaglandin release from lumbar disc and facet joint tissue. Spine 1994; 19: 206870.
  • 19
    Kang JD, Stefanovic-Racic M, McIntyre LA, Georgescu HI, Evans CH. Toward a biochemical understanding of human intervertebral disc degeneration and herniation: contributions of nitric oxide, interleukins, prostaglandin E2, and matrix metalloproteinases. Spine 1997; 22: 106573.
  • 20
    Kang SM, Schneider DB, Lin Z, Hanahan D, Dichek DA, Stock PG, et al. Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nat Med 1997; 3: 73843.
  • 21
    Igarashi T, Kikuchi S, Shubayev V, Myers RR. Exogenous tumor necrosis factor-α mimics nucleus pulposus-induced neuropathology: molecular, histologic, and behavioral comparisons in rats. Spine 2000; 25: 297580.
  • 22
    Olmarker K, Nutu M, Storkson R. Changes in spontaneous behavior in rats exposed to experimental disc herniation are blocked by selective TNF-α inhibition. Spine 2003; 28: 163541.
  • 23
    Doita M, Kanatani T, Harada T, Mizuno K. Immunohistologic study of the ruptured intervertebral disc of the lumbar spine. Spine 1996; 21: 23541.
  • 24
    Gronblad M, Virri J, Seitsalo S, Habtemariam A, Karaharju E. Inflammatory cells, motor weakness, and straight leg raising in transligamentous disc herniations. Spine 2000; 25: 28037.
  • 25
    Woertgen C, Rothoerl RD, Brawanski A. Influence of macrophage infiltration of herniated lumbar disc tissue on outcome after lumbar disc surgery. Spine 2000; 25: 8715.
  • 26
    Takada T, Nishida K, Doita M, Miyamoto H, Kurosaka M. Interleukin-6 production is upregulated by interaction between disc tissue and macrophages. Spine 2004; 29: 108992.
  • 27
    Mogil JS, Wilson SG, Bon K, Lee SE, Chung K, Raber P, et al. Heritability of nociception I: responses of 11 inbred mouse strains on 12 measures of nociception. Pain 1999; 80: 6782.
  • 28
    Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994; 53: 5563.
  • 29
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2math image Method. Methods 2001; 25: 4028.
  • 30
    Hou SX, Tang JG, Chen HS, Chen J. Chronic inflammation and compression of the dorsal root contribute to sciatica induced by the intervertebral disc herniation in rats. Pain 2003; 105: 25564.
  • 31
    Kawakami M, Tamaki T, Hashizume H, Weinstein JN, Meller ST. The role of phospholipase A2 and nitric oxide in pain-related behavior produced by an allograft of intervertebral disc material to the sciatic nerve of the rat. Spine 1997; 22: 10749.
  • 32
    Cunha FQ, Poole S, Lorenzetti BB, Ferreira SH. The pivotal role of tumour necrosis factor α in the development of inflammatory hyperalgesia. Br J Pharmacol 1992; 107: 6604.
  • 33
    Sorkin LS, Xiao WH, Wagner R, Myers RR. Tumour necrosis factor-α induces ectopic activity in nociceptive primary afferent fibres. Neuroscience 1997; 81: 25562.
  • 34
    Sachs D, Cunha FQ, Poole S, Ferreira SH. Tumour necrosis factor-α, interleukin-1β and interleukin-8 induce persistent mechanical nociceptor hypersensitivity. Pain 2002; 96: 8997.
  • 35
    Ferreira SH, Nakamura M. I. Prostaglandin hyperalgesia, a cAMP/Ca2+ dependent process. Prostaglandins 1979; 18: 17990.
  • 36
    England S, Bevan S, Docherty RJ. PGE2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade. J Physiol 1996; 495(Pt 2): 42940.
  • 37
    Schafers 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. Neurosci Lett 2003; 347: 17982.
  • 38
    O'Rielly DD, Loomis CW. Spinal prostaglandins facilitate exaggerated A- and C-fiber-mediated reflex responses and are critical to the development of allodynia early after L5-L6 spinal nerve ligation. Anesthesiology 2007; 106: 795805.
  • 39
    Nerlich AG, Weiler C, Zipperer J, Narozny M, Boos N. Immunolocalization of phagocytic cells in normal and degenerated intervertebral discs. Spine 2002; 27: 248490.
  • 40
    Haro H, Crawford HC, Fingleton B, MacDougall JR, Shinomiya K, Spengler DM, et al. Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption. J Clin Invest 2000; 105: 13341.
  • 41
    Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester GR. Macrophages in rheumatoid arthritis. Arthritis Res 2000; 2: 189202.
  • 42
    Grip O, Janciauskiene S, Lindgren S. Macrophages in inflammatory bowel disease. Curr Drug Targets Inflamm Allergy 2003; 2: 15560.
  • 43
    Ritchlin C. Psoriatic disease—from skin to bone. Nat Clin Pract Rheumatol 2007; 3: 698706.
  • 44
    Arias-Negrete S, Keller K, Chadee K. Proinflammatory cytokines regulate cyclooxygenase-2 mRNA expression in human macrophages. Biochem Biophys Res Commun 1995; 208: 5829.
  • 45
    Fournier T, Fadok V, Henson PM. Tumor necrosis factor-α inversely regulates prostaglandin D2 and prostaglandin E2 production in murine macrophages: synergistic action of cyclic AMP on cyclooxygenase-2 expression and prostaglandin E2 synthesis. J Biol Chem 1997; 272: 3106572.
  • 46
    Korhonen T, Karppinen J, Paimela L, Malmivaara A, Lindgren KA, 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: 275966.
  • 47
    Patrone JB, Bish SE, Stein DC. TNF-α-independent IL-8 expression: alterations in bacterial challenge dose cause differential human monocytic cytokine response. J Immunol 2006; 177: 131422.
  • 48
    Kosmadaki MG, Yaar M, Arble BL, Gilchrest BA. UV induces VEGF through a TNF-α independent pathway. FASEB J 2003; 17: 4468.
  • 49
    Kaplanski G, Fabrigoule M, Boulay V, Dinarello CA, Bongrand P, Kaplanski S, et al. Thrombin induces endothelial type II activation in vitro: IL-1 and TNF-α-independent IL-8 secretion and E-selectin expression. J Immunol 1997; 158: 543541.
  • 50
    Le Maitre CL, Hoyland JA, Freemont AJ. Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1β and TNFα expression profile. Arthritis Res Ther 2007; 9: R77.