New treatments and imaging strategies in degenerative disease of the intervertebral disks

Radiology

Volumn 264, Issue 1, 2012, Pages 6-19

  Lotz, Jeffrey C ^a   Haughton, Victor ^b   Boden, Scott D ^c   An, Howard S ^d   Kang, James D ^e   Masuda, Koichi ^f   Freemont, Anthony ^g   Berven, Sigurd ^h   Sengupta, Dilip K ⁱ   Tanenbaum, Lawrence ^j   Maurer, Philip ^k   Ranganathan, Arun ^l   Alavi, Abass ^m   Marinelli, Nicholas L ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d RUSH UNIVERSITY MEDICAL CENTER   (United States)

^e UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g UNIVERSITY OF MANCHESTER   (United Kingdom)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ DARTMOUTH HITCHCOCK MEDICAL CENTER   (United States)

^j NEW JERSEY NEUROSCIENCE INSTITUTE   (United States)

^k HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA   (United States)

^l University of Pennsylvania ^*  (United Kingdom)

^m UNIVERSITY OF PENNSYLVANIA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BETA GALACTOSIDASE; BONE MORPHOGENETIC PROTEIN; COMPLEMENTARY DNA; CONTRAST MEDIUM; EPIDERMAL GROWTH FACTOR; FIBROBLAST GROWTH FACTOR; INTERLEUKIN 1; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; LATENT MEMBRANE PROTEIN 1; MATRIX METALLOPROTEINASE INHIBITOR; OSTEOGENIC PROTEIN 1; PARVOVIRUS VECTOR; RECOMBINANT BONE MORPHOGENETIC PROTEIN 2; SOMATOMEDIN C; TRANSCRIPTION FACTOR SOX9;

BIOLOGICAL THERAPY; CLINICAL EVALUATION; DIAGNOSTIC IMAGING; DISCOGENIC PAIN; DRUG DIFFUSION; DRUG TARGETING; HUMAN; IMAGE ANALYSIS; INTERVERTEBRAL DISK DEGENERATION; INTERVERTEBRAL DISKECTOMY; LAMINECTOMY; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN SYNTHESIS INHIBITION; RELAXATION TIME; REVIEW; SIGNAL DETECTION; SPINE FUSION; VIRAL GENE THERAPY;

BIOMECHANICS; CONTRAST MEDIA; DIFFUSION MAGNETIC RESONANCE IMAGING; GENETIC THERAPY; HUMANS; INFLAMMATION MEDIATORS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; INTERVERTEBRAL DISC DEGENERATION; LOW BACK PAIN; MAGNETIC RESONANCE IMAGING; MAGNETIC RESONANCE SPECTROSCOPY; PAIN MEASUREMENT; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS; STEM CELL TRANSPLANTATION;

EID: 84862660554     PISSN: 00338419     EISSN: 15271315     Source Type: Journal    
DOI: 10.1148/radiol.12110339     Document Type: Review

References (155)

1. Sheehan NJ. Magnetic resonance imaging for low back pain: indications and limitations. Ann Rheum Dis 2010;69(1):7-11.
2. Deyo RA. Cascade effects of medical technology. Annu Rev Public Health 2002;23:23-44. (Pubitemid 34508065)
3. Lurie JD, Gerber PD, Sox HC. Clinical problem-solving: a pain in the back. N Engl J Med 2000;343(10):723-726.
4. Chou R, Qaseem A, Owens DK, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. Diagnostic imaging for low back pain: advice for high-value health care from the American College of Physicians. Ann Intern Med 2011;154(3):181-189.
5. Rubinstein SM, van Tulder M. A best-evidence review of diagnostic procedures for neck and low-back pain. Best Pract Res Clin Rheumatol 2008;22(3):471-482. (Pubitemid 351737280)
6. Koes BW, van Tulder M, Lin CW, 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(12):2075-2094.
7. Harkness EF, Macfarlane GJ, Silman AJ, McBeth J. Is musculoskeletal pain more common now than 40 years ago? two population-based cross-sectional studies. Rheumatology (Oxford) 2005;44(7):890-895. (Pubitemid 41511184)
8. Roberts S, Urban JP, Evans H, Eisenstein SM. Transport properties of the human cartilage endplate in relation to its composition and calcification. Spine (Phila Pa 1976) 1996;21(4):415-420.
9. Bernick S, Walker JM, Paule WJ. Age changes to the anulus fibrosus in human intervertebral discs. Spine (Phila Pa 1976) 1991;16(5):520-524.
10. Adams MA. Biomechanics of back pain. Acupunct Med 2004;22(4):178-188. (Pubitemid 40075251)
11. Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebral disc. Spine (Phila Pa 1976) 2004;29(23):2700-2709.
12. 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(10):961-971.
13. Sivan SS, Wachtel E, Tsitron E, et al. Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid. J Biol Chem 2008;283(14):8796-8801.
14. Bartels EM, Fairbank JC, Winlove CP, Urban JP. Oxygen and lactate concentrations measured in vivo in the intervertebral discs of patients with scoliosis and back pain. Spine (Phila Pa 1976) 1998;23(1):1-7; discussion 8.
15. Ejeskär A, Holm S. Oxygen tension measurements in the intervertebral disc: a methodological and experimental study. Ups J Med Sci 1979;84(1):83-93.
16. Zhao CQ, Wang LM, Jiang LS, Dai LY. The cell biology of intervertebral disc aging and degeneration. Ageing Res Rev 2007;6(3):247-261.
17. Freemont AJ. The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology (Oxford) 2009;48(1):5-10.
18. Anderson DG, Tannoury C. Molecular pathogenic factors in symptomatic disc degeneration. Spine J 2005;5(6 Suppl):260S-266S. (Pubitemid 41700070)
19. Roughley PJ. Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine (Phila Pa 1976) 2004;29(23):2691-2699.
20. Feng H, Danfelter M, Strömqvist B, Heinegård D. Extracellular matrix in disc degeneration. J Bone Joint Surg Am 2006;88(Suppl 2):25-29.
21. Roberts S, Evans H, Trivedi J, Menage J. Histology and pathology of the human intervertebral disc. J Bone Joint Surg Am 2006;88(Suppl 2):10-14.
22. Urban JP, Winlove CP. Pathophysiology of the intervertebral disc and the challenges for MRI. J Magn Reson Imaging 2007;25(2):419-432. (Pubitemid 46204589)
23. Adams MA, McNally DS, Dolan P. 'Stress'distributions inside intervertebral discs: the effects of age and degeneration. J Bone Joint Surg Br 1996;78(6):965-972. (Pubitemid 26392131)
24. Brown MF, Hukkanen MV, McCarthy ID, et al. Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease. J Bone Joint Surg Br 1997;79(1):147-153.
25. Ohtori S, Inoue G, Ito T, et al. Tumor necrosis factor-immunoreactive cells and PGP 9.5-immunoreactive nerve fibers in vertebral endplates of patients with discogenic low back pain and Modic type 1 or type 2 changes on MRI. Spine (Phila Pa 1976) 2006;31(9):1026-1031.
26. Peng B, Hao J, Hou S, et al. Possible pathogenesis of painful intervertebral disc degeneration. Spine (Phila Pa 1976) 2006;31(5):560-566.
27. Hilton RC, Ball J. Vertebral rim lesions in the dorsolumbar spine. Ann Rheum Dis 1984;43(2):302-307. (Pubitemid 14172582)
28. Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine (Phila Pa 1976) 2006;31(18):2151-2161.
29. Przybyla A, Pollintine P, Bedzinski R, Adams MA. Outer annulus tears have less effect than endplate fracture on stress distributions inside intervertebral discs: relevance to disc degeneration. Clin Biomech (Bristol, Avon) 2006;21(10):1013-1019. (Pubitemid 44691996)
30. Koeller W, Muehlhaus S, Meier W, Hartmann F. Biomechanical properties of human intervertebral discs subjected to axial dynamic compression - influence of age and degeneration. J Biomech 1986;19(10):807-816. (Pubitemid 17482050)
31. Paajanen H, Erkintalo M, Kuusela T, Dahlstrom S, Kormano M. Magnetic resonance study of disc degeneration in young low-back pain patients. Spine (Phila Pa 1976) 1989;14(9):982-985.
32. Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW. Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects: a prospective investigation. J Bone Joint Surg Am 1990;72(3):403-408. (Pubitemid 20151924)
33. Wand BM, O'Connell NE. Chronic non-specific low back pain: sub-groups or a single mechanism? BMC Musculoskelet Disord 2008;9:11.
34. Zhang YG, Guo TM, Guo X, Wu SX. Clinical diagnosis for discogenic low back pain. Int J Biol Sci 2009;5(7):647-658.
35. Manchikanti L, Singh V, Pampati V, et al. Evaluation of the relative contributions of various structures in chronic low back pain. Pain Physician 2001;4(4):308-316. (Pubitemid 33062069)
36. Kellgren JH. The anatomical source of back pain. Rheumatol Rehabil 1977;16(1):3-12. (Pubitemid 8046525)
37. Kuslich SD, Ulstrom CL, Michael CJ. The tissue origin of low back pain and sciatica: a report of pain response to tissue stimulation during operations on the lumbar spine using local anesthesia. Orthop Clin North Am 1991;22(2):181-187.
38. Luoma K, Riihimäki H, Luukkonen R, Raininko R, Viikari-Juntura E, Lamminen A. Low back pain in relation to lumbar disc degeneration. Spine (Phila Pa 1976) 2000;25(4):487-492.
39. Barrick WT, Schofferman JA, Reynolds JB, et al. Anterior lumbar fusion improves discogenic pain at levels of prior posterolateral fusion. Spine (Phila Pa 1976) 2000;25(7):853-857.
40. Pratsinis H, Kletsas D. Growth factors in intervertebral disc homeostasis. Connect Tissue Res 2008;49(3):273-276.
41. 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 (Phila Pa 1976) 1997;22(10):1065-1073.
42. Purmessur D, Freemont AJ, Hoyland JA. Expression and regulation of neurotrophins in the nondegenerate and degenerate human intervertebral disc. Arthritis Res Ther 2008;10(4):R99.
43. Johnson WE, Caterson B, Eisenstein SM, Hynds DL, Snow DM, Roberts S. Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis Rheum 2002;46(10):2658-2664. (Pubitemid 36118929)
44. Johnson WE, Sivan S, Wright KT, Eisenstein SM, Maroudas A, Roberts S. Human intervertebral disc cells promote nerve growth over substrata of human intervertebral disc aggrecan. Spine (Phila Pa 1976) 2006;31(11):1187-1193.
45. Freemont AJ, Peacock TE, Goupille P, Hoyland JA, O'Brien J, Jayson MI. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet 1997;350(9072):178-181. (Pubitemid 27303625)
46. Coppes MH, Marani E, Thomeer RT, Groen GJ. Innervation of "painful" lumbar discs. Spine (Phila Pa 1976) 1997;22(20):2342-2349; discussion 2349-2350.
47. Ulrich JA, Liebenberg EC, Thuillier DU, Lotz JC. ISSLS prize winner: repeated disc injury causes persistent inflammation. Spine (Phila Pa 1976) 2007;32(25):2812-2819.
48. Crock HV. Internal disc disruption: a challenge to disc prolapse fifty years on. Spine (Phila Pa 1976) 1986;11(6):650-653.
49. Olmarker K, Blomquist J, Strömberg J, Nannmark U, Thomsen P, Rydevik B. Inflammatogenic properties of nucleus pulposus. Spine (Phila Pa 1976) 1995;20(6):665-669.
50. Cavanaugh JM. Neural mechanism of idiopathic low back pain. In: Weinstein JN, Gordon SL, eds. Low back pain; a scientific and clinical overview. Rosemont, Ill: American Academy of Orthopaedic Surgeons, 1996.
51. Olmarker K, Larsson K. Tumor necrosis factor alpha and nucleus-pulposus-induced nerve root injury. Spine (Phila Pa 1976) 1998;23(23):2538-2544.
52. Olmarker K, Rydevik B. Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced thrombus formation, intraneural edema, and reduction of nerve conduction velocity: possible implications for future pharmacologic treatment strategies of sciatica. Spine (Phila Pa 1976) 2001;26(8):863-869.
53. Cuellar JM, Montesano PX, Carstens E. Role of TNF-alpha in sensitization of nociceptive dorsal horn neurons induced by application of nucleus pulposus to L5 dorsal root ganglion in rats. Pain 2004;110(3):578-587. (Pubitemid 39036789)
54. Ross JS, Modic MT, Masaryk TJ. Tears of the anulus fibrosus: assessment with Gd-DTPA-enhanced MR imaging. AJR Am J Roentgenol 1990;154(1):159-162. (Pubitemid 20029667)
55. Wolfer LR, Derby R, Lee JE, Lee SH. Systematic review of lumbar provocation discography in asymptomatic subjects with a meta-analysis of false-positive rates. Pain Physician 2008;11(4):513-538.
56. Carragee EJ, Alamin TF. Discography. a review. Spine J 2001;1(5):364-372.
57. Carragee EJ, Don AS, Hurwitz EL, Cuellar JM, Carrino JA, Herzog R. 2009 ISSLS Prize Winner. Does discography cause accelerated progression of degeneration changes in the lumbar disc: a ten-year matched cohort study. Spine (Phila Pa 1976) 2009;34(21):2338-2345.
58. Buttermann GR, Garvey TA, Hunt AF, et al. Lumbar fusion results related to diagnosis. Spine (Phila Pa 1976) 1998;23(1):116-127.
59. Modic MT, Ross JS. Lumbar degenerative disk disease. Radiology 2007;245(1):43-61. (Pubitemid 47417788)
60. Hicks GE, Morone N, Weiner DK. Degenerative lumbar disc and facet disease in older adults: prevalence and clinical correlates. Spine (Phila Pa 1976) 2009;34(12):1301-1306.
61. Quint U, Wilke HJ. Grading of degenerative disk disease and functional impairment: imaging versus patho-anatomical findings. Eur Spine J 2008;17(12):1705-1713.
62. Buttermann GR, Mullin WJ. Pain and disability correlated with disc degeneration via magnetic resonance imaging in scoliosis patients. Eur Spine J 2008;17(2):240-249.
63. Boos N, Semmer N, Elfering A, 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 (Phila Pa 1976) 2000;25(12):1484-1492.
64. Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976) 2001;26(17):1873-1878.
65. Haughton V. Don't you call me desiccated, J. Wellington Wimpy. AJNR Am J Neuroradiol 2010;31(9):1551.
66. Brown MD, Holmes DC, Heiner AD. Measurement of cadaver lumbar spine motion segment stiffness. Spine (Phila Pa 1976) 2002;27(9):918-922.
67. Johannessen W, Auerbach JD, Wheaton AJ, et al. Assessment of human disc degeneration and proteoglycan content using T1rho-weighted magnetic resonance imaging. Spine (Phila Pa 1976) 2006;31(11):1253-1257.
68. Fujiwara A, An HS, Lim TH, Haughton VM. Morphologic changes in the lumbar intervertebral foramen due to flexion-extension, lateral bending, and axial rotation: an in vitro anatomic and biomechanical study. Spine (Phila Pa 1976) 2001;26(8):876-882.
69. Ito M, Incorvaia KM, Yu SF, Fredrickson BE, Yuan HA, Rosenbaum AE. Predictive signs of discogenic lumbar pain on magnetic resonance imaging with discography correlation. Spine (Phila Pa 1976) 1998;23(11):1252-1258; discussion 1259-1260.
70. Cohen SP, Larkin TM, Barna SA, Palmer WE, Hecht AC, Stojanovic MP. Lumbar discography: a comprehensive review of outcome studies, diagnostic accuracy, and principles. Reg Anesth Pain Med 2005;30(2):163-183. (Pubitemid 40576221)
71. Zhou Y, Abdi S. Diagnosis and minimally invasive treatment of lumbar discogenic pain: a review of the literature. Clin J Pain 2006;22(5):468-481. (Pubitemid 44350457)
72. Weidenbaum M, Foster RJ, Best BA, et al. Correlating magnetic resonance imaging with the biochemical content of the normal human intervertebral disc. J Orthop Res 1992;10(4):552-561.
73. Tertti M, Paajanen H, Laato M, Aho H, Komu M, Kormano M. Disc degeneration in magnetic resonance imaging. A comparative biochemical, histologic, and radiologic study in cadaver spines. Spine (Phila Pa 1976) 1991;16(6):629-634.
74. Marinelli NL, Haughton VM, Muñoz A, Anderson PA. T2 relaxation times of intervertebral disc tissue correlated with water content and proteoglycan content. Spine (Phila Pa 1976) 2009;34(5):520-524.
75. Nightingale T, MacKay A, Pearce RH, Whittall KP, Flak B. A model of unloaded human intervertebral disk based on NMR relaxation. Magn Reson Med 2000;43(1):34-44. (Pubitemid 30027110)
76. Boos N, Wallin A, Gbedegbegnon T, Aebi M, Boesch C. Quantitative MR imaging of lumbar intervertebral disks and vertebral bodies: influence of diurnal water content variations. Radiology 1993;188(2): 351-354. (Pubitemid 23216251)
77. Paajanen H, Lehto I, Alanen A, Erkintalo M, Komu M. Diurnal fluid changes of lumbar discs measured indirectly by magnetic resonance imaging. J Orthop Res 1994;12(4):509-514. (Pubitemid 24266644)
78. Jenkins JPR, Hickey DS, Zhu XP, Machin M, Isherwood I. MR imaging of the intervertebral disc: a quantitative study. Br J Radiol 1985;58(692):705-709. (Pubitemid 15238856)
79. Marinelli NL, Haughton VM, Anderson PA. T2 relaxation times correlated with stage of lumbar intervertebral disk degeneration and patient age. AJNR Am J Neuroradiol 2010;31(7):1278-1282.
80. Watanabe A, Benneker LM, Boesch C, Watanabe T, Obata T, Anderson SE. Classification of intervertebral disk degeneration with axial T2 mapping. AJR Am J Roentgenol 2007;189(4):936-942. (Pubitemid 47479779)
81. Kerttula L, Kurunlahti M, Jauhiainen J, Koivula A, Oikarinen J, Tervonen O. Apparent diffusion coefficients and T2 relaxation time measurements to evaluate disc degeneration: a quantitative MR study of young patients with previous vertebral fracture. Acta Radiol 2001;42(6):585-591. (Pubitemid 33655107)
82. Boos N, Wallin A, Schmucker T, Aebi M, Boesch C. Quantitative MR imaging of lumbar intervertebral disc and vertebral bodies: methodology, reproducibility, and preliminary results. Magn Reson Imaging 1994;12(4):577-587. (Pubitemid 24183120)
83. Chiu EJ, Newitt DC, Segal MR, Hu SS, Lotz JC, Majumdar S. Magnetic resonance imaging measurement of relaxation and water diffusion in the human lumbar intervertebral disc under compression in vitro. Spine (Phila Pa 1976) 2001;26(19):E437-E444.
84. Antoniou J, Pike GB, Steffen T, et al. Quantitative magnetic resonance imaging in the assessment of degenerative disc disease. Magn Reson Med 1998;40(6):900-907. (Pubitemid 28543842)
85. Boos N, Dreier D, Hilfiker E, et al. Tissue characterization of symptomatic and asymptomatic disc herniations by quantitative magnetic resonance imaging. J Orthop Res 1997;15(1):141-149. (Pubitemid 27111213)
86. Li X, Han ET, Ma CB, Link TM, Newitt DC, Majumdar S. In vivo 3T spiral imaging based multi-slice T(1rho) mapping of knee cartilage in osteoarthritis. Magn Reson Med 2005;54(4):929-936. (Pubitemid 41457065)
87. Lozano J, Li X, Link TM, Safran M, Majumdar S, Ma CB. Detection of posttraumatic cartilage injury using quantitative T1rho magnetic resonance imaging. A report of two cases with arthroscopic findings. J Bone Joint Surg Am 2006;88(6):1349-1352. (Pubitemid 43837133)
88. Borthakur A, Mellon E, Niyogi S, Witschey W, Kneeland JB, Reddy R. Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage. NMR Biomed 2006;19(7):781-821. (Pubitemid 44811543)
89. Regatte RR, Akella SV, Borthakur A, Kneeland JB, Reddy R. Proteoglycan depletioninduced changes in transverse relaxation maps of cartilage: comparison of T2 and T1rho. Acad Radiol 2002;9(12):1388-1394. (Pubitemid 36331013)
90. Nguyen AM, Johannessen W, Yoder JH, et al. Noninvasive quantification of human nucleus pulposus pressure with use of T1rhoweighted magnetic resonance imaging. J Bone Joint Surg Am 2008;90(4):796-802. (Pubitemid 351499969)
91. Auerbach JD, Johannessen W, Borthakur A, et al. In vivo quantification of human lumbar disc degeneration using T(1rho)-weighted magnetic resonance imaging. Eur Spine J 2006;15(Suppl 3):S338-S344. (Pubitemid 44371012)
92. Borthakur A, Maurer PM, Fenty M, et al. T1r magnetic resonance imaging and discography pressure as novel biomarkers for disc degeneration and low back pain. Spine (Phila Pa 1976) 2011;36(25):2190-2196.
93. Arun R, Freeman BJ, Scammell BE, Mc-Nally DS, Cox E, Gowland P. 2009 ISSLS Prize Winner. What influence does sustained mechanical load have on diffusion in the human intervertebral disc? an in vivo study using serial postcontrast magnetic resonance imaging. Spine (Phila Pa 1976) 2009;34(21):2324-2337.
94. Rajasekaran S, Babu JN, Arun R, Armstrong BR, Shetty AP, Murugan S. ISSLS Prize Winner. A study of diffusion in human lumbar discs: a serial magnetic resonance imaging study documenting the influence of the endplate on diffusion in normal and degenerate discs. Spine (Phila Pa 1976) 2004;29(23):2654-2667.
95. Ibrahim MA, Haughton VM, Hyde JS. Effect of disk maturation on diffusion of low-molecular-weight gadolinium complexes: an experimental study in rabbits. AJNR Am J Neuroradiol 1995;16(6):1307-1311.
96. Rajasekaran S, Vidyadhara S, Subbiah M, et al. ISSLS Prize Winner. A study of effects of in vivo mechanical forces on human lumbar discs with scoliotic disc as a biological model: results from serial postcontrast diffusion studies, histopathology and biochemical analysis of twenty-one human lumbar scoliotic discs. Spine (Phila Pa 1976) 2010;35(21):1930-1943.
97. Rajasekaran S, Venkatadass K, Naresh Babu J, Ganesh K, Shetty AP. Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs: results from in-vivo serial post-contrast MRI studies in 365 human lumbar discs. Eur Spine J 2008;17(5):626-643.
98. Freemont AJ, Watkins A, Le Maitre C, Jeziorska M, Hoyland JA. Current understanding of cellular and molecular events in intervertebral disc degeneration: implications for therapy. J Pathol 2002;196(4):374-379. (Pubitemid 34262847)
99. Ishii T, Tsuji H, Sano A, Katoh Y, Matsui H, Terahata N. Histochemical and ultrastructural observations on brown degeneration of human intervertebral disc. J Orthop Res 1991;9(1):78-90.
100. Bibby SR, Jones DA, Lee RB, Yu J, Urban JPG. The pathophysiology of the intervertebral disc. Joint Bone Spine 2001;68(6):537-542. (Pubitemid 34037288)
101. Diamant B, Karlsson J, Nachemson A. Correlation between lactate levels and pH in discs of patients with lumbar rhizopathies. Experientia 1968;24(12):1195-1196.
102. Nachemson A. Intradiscal measurements of pH in patients with lumbar rhizopathies. Acta Orthop Scand 1969;40(1):23-42.
103. Keshari KR, Lotz JC, Link TM, Hu SS, Majumdar S, Kurhanewicz J. Lactic acid and proteoglycans as metabolic markers for discogenic back pain. Spine (Phila Pa 1976) 2008;33(3):312-317.
104. Hu S, Peacock J, Claude J, et al. Modified magnetic resonance spectroscopy diagnosis of painful and non-painful lumbar intervertebral discs. Presented at the 2010 Annual Meeting of the Orthopaedic Research Society, 2010.
105. Zhuang H, Yu JQ, Alavi A. Applications of fluorodeoxyglucose-PET imaging in the detection of infection and inflammation and other benign disorders. Radiol Clin North Am 2005;43(1):121-134. (Pubitemid 40326564)
106. Grant FD, Fahey FH, Packard AB, Davis RT, Alavi A, Treves ST. Skeletal PET with 18F-fluoride: applying new technology to an old tracer. J Nucl Med 2008;49(1):68-78.
107. Basu S, Kumar R, Alavi A. PET and PETCT imaging in infection and inflammation: its critical role in assessing complications related to therapeutic interventions in patients with cancer. Indian J Cancer 2010;47(4):371-379.
108. Basu S, Zaidi H, Houseni M, et al. Novel quantitative techniques for assessing regional and global function and structure based on modern imaging modalities: implications for normal variation, aging and diseased states. Semin Nucl Med 2007;37(3):223-239. (Pubitemid 46533824)
109. Masuda K, Oegema TR Jr, An HS. Growth factors and treatment of intervertebral disc degeneration. Spine (Phila Pa 1976) 2004;29(23):2757-2769.
110. Gruber HE, Norton HJ, Hanley EN Jr. Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro. Spine (Phila Pa 1976) 2000;25(17):2153-2157.
111. 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(1):13-21. (Pubitemid 27381676)
112. Okuda S, Nakase T, Yonenobu K, Ono K. Age-dependent expression of transforming growth factor beta1 (TGF-beta1) and its receptors and age-related stimulatory effect of TGF-beta1 on proteoglycan synthesis in rat intervertebral discs. J Muscle Res 2000;4(3):151-159. (Pubitemid 32249017)
113. Thompson JP, Oegema TR Jr, Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine (Phila Pa 1976) 1991;16(3):253-260.
114. Kim DJ, Moon SH, Kim H, et al. Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells. Spine (Phila Pa 1976) 2003;28(24):2679-2684.
115. Tim Yoon S, Su Kim K, Li J, et al. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro. Spine (Phila Pa 1976) 2003;28(16):1773-1780.
116. Masuda K, Takegami K, An H, et al. Recombinant osteogenic protein-1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads. J Orthop Res 2003;21(5):922-930. (Pubitemid 37045572)
117. An HS, Takegami K, Kamada H, et al. Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine (Phila Pa 1976) 2005;30(1):25-31; discussion 31-32.
118. Zhang Y, An HS, Song S, et al. Growth factor osteogenic protein-1: differing effects on cells from three distinct zones in the bovine intervertebral disc. Am J Phys Med Rehabil 2004;83(7):515-521. (Pubitemid 38802321)
119. Masuda K, Imai Y, Okuma M, et al. Osteogenic protein-1 injection into a degenerated disc induces the restoration of disc height and structural changes in the rabbit anular puncture model. Spine (Phila Pa 1976) 2006;31(7):742-754.
120. Miyamoto K, Masuda K, Kim JG, et al. Intradiscal injections of osteogenic protein-1 restore the viscoelastic properties of degenerated intervertebral discs. Spine J 2006;6(6):692-703. (Pubitemid 44660878)
121. Imai Y, Okuma M, An HS, et al. Restoration of disc height loss by recombinant human osteogenic protein-1 injection into intervertebral discs undergoing degeneration induced by an intradiscal injection of chondroitinase ABC. Spine (Phila Pa 1976) 2007;32(11):1197-1205.
122. Chujo T, An HS, Akeda K, et al. Effects of growth differentiation factor-5 on the intervertebral disc - in vitro bovine study and in vivo rabbit disc degeneration model study. Spine (Phila Pa 1976) 2006;31(25):2909-2917.
123. Zhang Y, An HS, Thonar EJ, Chubinskaya S, He TC, Phillips FM. Comparative effects of bone morphogenetic proteins and sox9 overexpression on extracellular matrix metabolism of bovine nucleus pulposus cells. Spine (Phila Pa 1976) 2006;31(19):2173-2179.
124. Shinmei M, Kikuchi T, Yamagishi M, Shimomura Y. The role of interleukin-1 on proteoglycan metabolism of rabbit annulus fibrosus cells cultured in vitro. Spine (Phila Pa 1976) 1988;13(11):1284-1290.
125. Le Maitre CL, Freemont AJ, Hoyland JA. The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Res Ther 2005;7(4):R732-R745.
126. Le Maitre CL, Freemont AJ, Hoyland JA. A preliminary in vitro study into the use of IL-1Ra gene therapy for the inhibition of intervertebral disc degeneration. Int J Exp Pathol 2006;87(1):17-28.
127. Le Maitre CL, Hoyland JA, Freemont AJ. Interleukin-1 receptor antagonist delivered directly and by gene therapy inhibits matrix degradation in the intact degenerate human intervertebral disc: an in situ zymographic and gene therapy study. Arthritis Res Ther 2007;9(4):R83.
128. Bachmeier BE, Nerlich AG, Weiler C, Paesold G, Jochum M, Boos N. Analysis of tissue distribution of TNF-alpha, TNF-alpha-receptors, and the activating TNF-alpha-converting enzyme suggests activation of the TNF-alpha system in the aging intervertebral disc. Ann N Y Acad Sci 2007;1096:44-54. (Pubitemid 47092497)
129. Le Maitre CL, Hoyland JA, Freemont AJ. Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile. Arthritis Res Ther 2007;9(4):R77.
130. Weiler C, Nerlich AG, Bachmeier BE, Boos N. Expression and distribution of tumor necrosis factor alpha in human lumbar intervertebral discs: a study in surgical specimen and autopsy controls. Spine (Phila Pa 1976) 2005;30(1):44-53; discussion 54.
131. Ellman MB, An HS, Muddasani P, Im HJ. Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis. Gene 2008;420(1):82-89.
132. Wallach CJ, Sobajima S, Watanabe Y, et al. Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Spine (Phila Pa 1976) 2003;28(20):2331-2337.
133. Evans C. Potential biologic therapies for the intervertebral disc. J Bone Joint Surg Am 2006;88(Suppl 2):95-98.
134. Evans CH, Robbins PD. Possible orthopaedic applications of gene therapy. J Bone Joint Surg Am 1995;77(7):1103-1114.
135. Robbins PD, Ghivizzani SC. Viral vectors for gene therapy. Pharmacol Ther 1998;80(1):35-47. (Pubitemid 28498200)
136. Hubert MG, Vadala G, Sowa G, Studer RK, Kang JD. Gene therapy for the treatment of degenerative disk disease. J Am Acad Orthop Surg 2008;16(6):312-319.
137. Sobajima S, Kim JS, Gilbertson LG, Kang JD. Gene therapy for degenerative disc disease. Gene Ther 2004;11(4): 390-401. (Pubitemid 38263089)
138. Nishida K, Kang JD, Suh JK, Robbins PD, Evans CH, Gilbertson LG. Adenovirus-mediated gene transfer to nucleus pulposus cells. Implications for the treatment of intervertebral disc degeneration. Spine (Phila Pa 1976) 1998;23(22):2437-2442; discussion 2443.
139. Nishida K, Kang JD, Gilbertson LG, et al. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene. Spine (Phila Pa 1976) 1999;24(23):2419-2425.
140. Yoon ST, Park JS, Kim KS, et al. ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of proteoglycans and BMPs in vitro and in vivo. Spine (Phila Pa 1976) 2004;29(23):2603-2611.
141. Vadalà G, Studer RK, Sowa G, et al. Coculture of bone marrow mesenchymal stem cells and nucleus pulposus cells modulate gene expression profile without cell fusion. Spine (Phila Pa 1976) 2008;33(8):870-876.
142. Vadalà G, Sobajima S, Lee JY, et al. In vitro interaction between muscle-derived stem cells and nucleus pulposus cells. Spine J 2008;8(5):804-809.
143. Yamamoto Y, Mochida J, Sakai D, et al. Upregulation of the viability of nucleus pulposus cells by bone marrow-derived stromal cells: significance of direct cell-to-cell contact in coculture system. Spine (Phila Pa 1976) 2004;29(14):1508-1514.
144. Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG, Kang JD. Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 2008;8(6):888-896.
145. Sobajima S, Kompel JF, Kim JS, et al. A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology. Spine (Phila Pa 1976) 2005;30(1):15-24.
146. Sakai D, Mochida J, Iwashina T, et al. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 2006;27(3):335-345. (Pubitemid 41457236)
147. Nomura T, Mochida J, Okuma M, Nishimura K, Sakabe K. Nucleus pulposus allograft retards intervertebral disc degeneration. Clin Orthop Relat Res 2001 (389):94-101. (Pubitemid 32729644)
148. Zhang Y, Li Z, Thonar EJ, et al. Transduced bovine articular chondrocytes affect the metabolism of cocultured nucleus pulposus cells in vitro: implications for chondrocyte transplantation into the intervertebral disc. Spine (Phila Pa 1976) 2005;30(23):2601-2607.
149. Ganey T, Hutton WC, Moseley T, Hedrick M, Meisel HJ. Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: experiments in a canine model. Spine (Phila Pa 1976) 2009;34(21):2297-2304.
150. Anderson DG, Albert TJ, Fraser JK, et al. Cellular therapy for disc degeneration. Spine (Phila Pa 1976) 2005;30(17 Suppl):S14-S19.
151. National Center for Health Statistics. Health, United States, 2006: With chart-book on trends in the health of Americans. Hyattsville, Md: National Center for Health Statistics, 2006.
152. Katz JN. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J Bone Joint Surg Am 2006;88(Suppl 2):21-24.
153. Croft PR, Macfarlane GJ, Papageorgiou AC, Thomas E, Silman AJ. Outcome of low back pain in general practice: a prospective study. BMJ 1998;316(7141):1356-1359. (Pubitemid 28195877)
154. Henschke N, Maher CG, Refshauge KM, Das A, McAuley JH. Low back pain research priorities: a survey of primary care practitioners. BMC Fam Pract 2007;8:40.
155. Bornstein BH, Emler AC. Rationality in medical decision making: a review of the literature on doctors' decision-making biases. J Eval Clin Pract 2001;7(2):97-107. (Pubitemid 32489003)