Intervertebral Disc Degeneration & Aging
Introduction
Disc degeneration describes a condition where intervertebral discs in the spine wear out over time. Intervertebral discs are the shock-absorbers between the vertebral bodies in the spine that give the spine its great flexibility. As we all get older, it is normal for the discs to slowly lose height, become stiffer and wear out. Not everyone will develop symptoms from this normal process of aging. In some people the process of disc aging and degeneration occurs at a younger age or at a more rapid rate. Some of these patients will develop pain or other symptoms as a result of the disc degeneration.
Clinically relevant outcomes of intervertebral disc degeneration include back pain and sciatica, or radiculopathy, secondary to neural compression. When symptoms become chronic and unresponsive to treatments, chronic pain, permanent disability, with reduced quality of life, can occurs.
Low back pain can be caused by the degenerative disc itself, termed discogenic pain(1-5), however, the exact pain generator may be difficult to identify in some patients(6). 75-80% of people will experience low back pain at some stage with a prevalence ranging from 15-45%(7), whilst severe disc degeneration is associated with a two-fold increase in chronic lower back pain(8, 9).
Despite low back pain being strongly linked to disc degeneration(1-5), it is well recognised that not all patients with radiological evidence of disc degeneration, or disc aging, will have symptoms. Most patients with disc degeneration do not require surgery or invasive treatments. Initial treatments include conservative therapies such as analgesics, physical therapies and multimodal pain management strategies.
For more information about back pain watch the video below.
Introduction
Disc degeneration describes a condition where intervertebral discs in the spine wear out over time. Intervertebral discs are the shock-absorbers between the vertebral bodies in the spine that give the spine its great flexibility. As we all get older, it is normal for the discs to slowly lose height, become stiffer and wear out. Not everyone will develop symptoms from this normal process of aging. In some people the process of disc aging and degeneration occurs at a younger age or at a more rapid rate. Some of these patients will develop pain or other symptoms as a result of the disc degeneration.
Clinically relevant outcomes of intervertebral disc degeneration include back pain and sciatica, or radiculopathy, secondary to neural compression. When symptoms become chronic and unresponsive to treatments, chronic pain, permanent disability, with reduced quality of life, can occurs.
Low back pain can be caused by the degenerative disc itself, termed discogenic pain(1-5), however, the exact pain generator may be difficult to identify in some patients(6). 75-80% of people will experience low back pain at some stage with a prevalence ranging from 15-45%(7), whilst severe disc degeneration is associated with a two-fold increase in chronic lower back pain(8, 9).
Despite low back pain being strongly linked to disc degeneration(1-5), it is well recognised that not all patients with radiological evidence of disc degeneration, or disc aging, will have symptoms. Most patients with disc degeneration do not require surgery or invasive treatments. Initial treatments include conservative therapies such as analgesics, physical therapies and multimodal pain management strategies.
For more information about back pain watch the video below.
In addition to back pain, disc degeneration can lead to disc prolapse and symptom due to neural compression. Disc degeneration is thought to be the precipitating cause of most degenerative conditions affecting the lumbar spine.
The following provides more detailed information about he process of disc degeneration. It is aimed at other health professionals, researchers and patients seeking to know more about the process of degeneration.
What Causes Disc Degeneration
Multiple cellular, biochemical and mechanical failures occur in the complex process of lumbar disc degeneration (LDD). The aetiology of disc aging and degeneration is complex and multifactorial, involving genetic, nutritional and mechanical factors(10), the result of which leads to changes in both the cellular and matrix components of the disc. An imbalance between extracellular matrix degradation and synthesis results in progressive failure of the disc with altered biomechanics at the affected spinal level. Disc degeneration is a progressive process, as the disc has limited ability for self-repair.
1. Mechanical Effects and disc injury
It seems logical that abnormal loading of the intervertebral disc would cause injury and subsequent degeneration. Disc degeneration appears more common in patients who perform repetitive physical work which constantly stresses the spine. Obesity has also been strongly linked to disc degeneration, with discs chronically overloaded by excessive body weight, and lacking support from weakened muscles secondary to sedentary lifestyles(11).
2. Genetics Effects
Numerous studies have confirmed a high familial predisposition to disc degeneration(12-16). Twin studies revealed an overall heritability of up to 75%(16-18), whilst Patel et al demonstrated a significantly elevated risk of developing degeneration in first (RR 4.15, P<0.001) and third-degree relatives (RR 1.46, P=0.027)(14). Genetic effects become more evident as age progresses and are affected by environmental influences, such as smoking and trauma(19). Gene polymorphisms involving genes encoding for aggrecan, collagens (I, II, IX), pro-inflammatory cytokine interleukin-1(IL-1), and matrix degrading enzymes, such as matrix-metalloproteinase-3 (MMP-3), have been implicated in the degenerative process(20-25).
3. Nutritional Influences on the disc
Inadequate supply of nutrients is an important factor contributing to LDD.
The intervertebral disc is essentially avascular, except for at the outer annular regions, and cells are dependent on diffusion of oxygen and metabolites across endplates and matrix tissue for adequate nutrition. The central nucleus pulposus cells are especially vulnerable to insult. A metabolite gradient exists throughout the disc with minimal nutrients (glucose, oxygen) and high levels of lactic acid present within central regions(26). With degeneration, this metabolite gradient is exaggerated influencing the degenerative process. When the tenuous nutrient supply is reduced, cell death and altered matrix production ensue, establishing a vicious cycle of cell compromise, matrix degradation and endplate changes, leading to further cell compromise, and subsequent advancement of degeneration.
Cigarette smoking, diabetes mellitus and atheroma can contribute to the development and progression of disc degeneration(27, 28).
What happens to discs during the process of aging and degeneration?
1. Cellular Changes
Approximately 1% of the intervertebral disc consistants of cartilage producing cells called chondrocytes. Overall there is a decrease in disc cell density and increased senescence of the cartilage cells(29, 30). Loss of appropriately functioning cells, due to both necrosis and apoptosis, is present in both aging biology and matrix production.
The loss of notochordal cells, which occurs with normal development in humans, and other chondrodystrophoid species, contributes to the degenerative process.
2. Disc Matrix Changes
Alterations in disc cell number and function, and cellular responses to nutritional deficiencies in turn leads to alterations in both the cartilaginous and proteoglycan matrix components of the disc. Proteoglycan (PG) loss occurs due to their decreased production by senescent disc cells and through increased expression of proteolytic enzymes(31-33). Loss of pivotal water-binding proteoglycan molecules leads to dehydration and collapse of the disc.
Changes in the collagenous matrix components also occur leading to fibrosis of the disc. Alterations in the constituents of the matrix and decreased water content results in decreased flexibility and altered load distribution leading to cleft and fissure formation in both the NP and AF(30, 34).
3. Endplate and Vertebral Body Changes
Bony endplate changes occur with thinning, calcification and alterations in vascularity, leading to a decreased ability for diffusion of nutrients and waste products of disc metabolism.
Change within the adjacent vertebral bodies also occurs, with evidence of sclerosis and bone micro-fracture(30). Osteophytes can also develop from the margins of the vertebral bodies and contribute to neural compression(35).
In addition, degenerative changes are also evident in the corresponding facet joints, suggesting that disc degeneration is the primary event leading to the clinical condition of degenerative spondylosis(36).
4. Neural and Vascular Changes
As disc degeneration progresses neo-vascularisation (blood vessel growth), with concurrent neo-innervation (nerve growth), can occur within the degenerative disc(5, 37, 38).
With the loss of the water binding PGs from the disc, its capacity to absorb and efficiently distribute weight axial and rotational loads is diminished, resulting in additional mechanical stresses leading to concentric and radiating tears that may in the disc(12, 35, 39-41). These structural events are considered to provoke the proliferation and migration of blood vessels and nerve fibres, normally confined to the periphery of the disc, to the deeper regions of the disc(5, 12). The establishment of these extended nerve fibers has been cited as a major cause of chronic lower back pain in degenerate discs(4, 5, 42).
In addition to the nociceptive neural mediated pain, local production of cytokines (IL-1, IL-6, TNF-α), growth factors and other immuno-modulatory pro-inflammatory peptides (leukotriene B4, prostaglandin E2) within the degenerative disc, can contribute to, and augment, discogenic pain(10, 43).
5. Mechanical Changes
The alterations in disc matrix which occurs with degeneration ultimately leads to abnormal biomechanics at the affected level(44). The inability of the disc to function as a normal intervertebral motion segment and load distributor has critical implications for accelerating degeneration at both the affected level and adjacent levels, as well as precipitating pain in abnormally loaded structures, such as facet joints, ligaments and paraspinal musculature.
6. Morphological Features of Disc Degeneration
Disc degeneration disrupts the normal architecture of the disc to varying degrees, the most severe of which leads to complete collapse of the disc with loss of distinction between annulus fibrosus and nucleus pulposus. Eventually ankylosis or auto-fusion of the spinal motion segment can occur.
7. Radiological Features of Disc Degeneration
Radiographic imaging plays a crucial role in the clinical assessment of back pain, disc degeneration and other spinal pathologies. Magnetic Resonance Imaging (MRI), with its ability to accurately demonstrate disc morphology and hydration state, is now the “gold standard” imaging modality used to assess disc disease with smaller roles for computed tomography (CT) and plain X-ray imaging(45). An understanding of the imaging characteristics is crucial as they are endpoints commonly employed by researchers to determine the efficacy of biological treatments.
References
1. van Tulder MW, Assendelft WJ, Koes BW, Bouter LM. Spinal radiographic findings and nonspecific low back pain. A systematic review of observational studies. Spine (Phila Pa 1976). 1997;22(4):427-34.
2. de Schepper EI, Damen J, van Meurs JB, Ginai AZ, Popham M, Hofman A, et al. The association between lumbar disc degeneration and low back pain: the influence of age, gender, and individual radiographic features. Spine (Phila Pa 1976). 2010;35(5):531-6.
3. Takatalo J, Karppinen J, Niinimaki J, Taimela S, Nayha S, Mutanen P, et al. Does lumbar disc degeneration on magnetic resonance imaging associate with low back symptom severity in young Finnish adults? Spine. 2011;36(25):2180-9.
4. Luoma K, Riihimaki H, Luukkonen R, Raininko R, Viikari-Juntura E, Lamminen A. Low back pain in relation to lumbar disc degeneration. Spine. 2000;25(4):487-92.
5. Brisby H. Pathology and possible mechanisms of nervous system response to disc degeneration. The Journal of bone and joint surgery American volume. 2006;88 Suppl 2:68-71.
6. Deyo RA, Weinstein JN. Low back pain. The New England journal of medicine. 2001;344(5):363-70.
7. Andersson GB. Epidemiological features of chronic low-back pain. Lancet. 1999;354(9178):581-5.
8. Hicks GE, Morone N, Weiner DK. Degenerative lumbar disc and facet disease in older adults: prevalence and clinical correlates. Spine. 2009;34(12):1301-6.
9. Takatalo J, Karppinen J, Niinimaki J, Taimela S, Nayha S, Mutanen P, et al. Does lumbar disc degeneration on MRI associate with low back symptom severity in young Finnish adults? Spine (Phila Pa 1976). 2011.
10. Paesold G, Nerlich AG, Boos N. Biological treatment strategies for disc degeneration: potentials and shortcomings. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2007;16(4):447-68.
11. Shiri R, Karppinen J, Leino-Arjas P, Solovieva S, Viikari-Juntura E. The association between obesity and low back pain: a meta-analysis. American journal of epidemiology. 2010;171(2):135-54.
12. Melrose J, Smith SM, Little CB, Moore RJ, Vernon-Roberts B, Fraser RD. Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2008;17(9):1131-48.
13. Matsui H, Kanamori M, Ishihara H, Yudoh K, Naruse Y, Tsuji H. Familial predisposition for lumbar degenerative disc disease. A case-control study. Spine (Phila Pa 1976). 1998;23(9):1029-34.
14. Patel AA, Spiker WR, Daubs M, Brodke D, Cannon-Albright LA. Evidence for an inherited predisposition to lumbar disc disease. J Bone Joint Surg Am. 2011;93(3):225-9.
15. Livshits G, Cohen Z, Higla O, Yakovenko K. Familial history, age and smoking are important risk factors for disc degeneration disease in Arabic pedigrees. European journal of epidemiology. 2001;17(7):643-51.
16. Williams FM, Popham M, Sambrook PN, Jones AF, Spector TD, MacGregor AJ. Progression of lumbar disc degeneration over a decade: a heritability study. Ann Rheum Dis. 2011;70(7):1203-7.
17. MacGregor AJ, Andrew T, Sambrook PN, Spector TD. Structural, psychological, and genetic influences on low back and neck pain: a study of adult female twins. Arthritis and rheumatism. 2004;51(2):160-7.
18. Battie MC, Videman T, Levalahti E, Gill K, Kaprio J. Genetic and environmental effects on disc degeneration by phenotype and spinal level: a multivariate twin study. Spine (Phila Pa 1976). 2008;33(25):2801-8.
19. Uei H, Matsuzaki H, Oda H, Nakajima S, Tokuhashi Y, Esumi M. Gene expression changes in an early stage of intervertebral disc degeneration induced by passive cigarette smoking. Spine (Phila Pa 1976). 2006;31(5):510-4.
20. Solovieva S, Kouhia S, Leino-Arjas P, Ala-Kokko L, Luoma K, Raininko R, et al. Interleukin 1 polymorphisms and intervertebral disc degeneration. Epidemiology. 2004;15(5):626-33.
21. Solovieva S, Leino-Arjas P, Saarela J, Luoma K, Raininko R, Riihimaki H. Possible association of interleukin 1 gene locus polymorphisms with low back pain. Pain. 2004;109(1-2):8-19.
22. Kawaguchi Y, Osada R, Kanamori M, Ishihara H, Ohmori K, Matsui H, et al. Association between an aggrecan gene polymorphism and lumbar disc degeneration. Spine (Phila Pa 1976). 1999;24(23):2456-60.
23. Noponen-Hietala N, Kyllonen E, Mannikko M, Ilkko E, Karppinen J, Ott J, et al. Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis. Ann Rheum Dis. 2003;62(12):1208-14.
24. Pluijm SM, van Essen HW, Bravenboer N, Uitterlinden AG, Smit JH, Pols HA, et al. Collagen type I alpha1 Sp1 polymorphism, osteoporosis, and intervertebral disc degeneration in older men and women. Ann Rheum Dis. 2004;63(1):71-7.
25. 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. J Bone Joint Surg Br. 2001;83(4):491-5.
26. Holm S, Maroudas A, Urban JP, Selstam G, Nachemson A. Nutrition of the intervertebral disc: solute transport and metabolism. Connect Tissue Res. 1981;8(2):101-19.
27. Oda H, Matsuzaki H, Tokuhashi Y, Wakabayashi K, Uematsu Y, Iwahashi M. Degeneration of intervertebral discs due to smoking: experimental assessment in a rat-smoking model. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. 2004;9(2):135-41.
28. Kurunlahti M, Tervonen O, Vanharanta H, Ilkko E, Suramo I. Association of atherosclerosis with low back pain and the degree of disc degeneration. Spine (Phila Pa 1976). 1999;24(20):2080-4.
29. Kim KW, Chung HN, Ha KY, Lee JS, Kim YY. Senescence mechanisms of nucleus pulposus chondrocytes in human intervertebral discs. Spine J. 2009;9(8):658-66.
30. Roberts S, Evans H, Trivedi J, Menage J. Histology and pathology of the human intervertebral disc. The Journal of bone and joint surgery American volume. 2006;88 Suppl 2:10-4.
31. Roberts S, Caterson B, Menage J, Evans EH, Jaffray DC, Eisenstein SM. Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc. Spine. 2000;25(23):3005-13.
32. Pockert AJ, Richardson SM, Le Maitre CL, Lyon M, Deakin JA, Buttle DJ, et al. Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration. Arthritis and rheumatism. 2009;60(2):482-91.
33. Bachmeier BE, Nerlich A, Mittermaier N, Weiler C, Lumenta C, Wuertz K, et al. Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration. Eur Spine J. 2009;18(11):1573-86.
34. Urban JP, Roberts S. Degeneration of the intervertebral disc. Arthritis research & therapy. 2003;5(3):120-30.
35. Vernon-Roberts B, Pirie CJ. Degenerative changes in the intervertebral discs of the lumbar spine and their sequelae. Rheumatology and rehabilitation. 1977;16(1):13-21.
36. Moore RJ, Crotti TN, Osti OL, Fraser RD, Vernon-Roberts B. Osteoarthrosis of the facet joints resulting from anular rim lesions in sheep lumbar discs. Spine. 1999;24(6):519-25.
37. Ozaki S, Muro T, Ito S, Mizushima M. Neovascularization of the outermost area of herniated lumbar intervertebral discs. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. 1999;4(4):286-92.
38. Pai RR, D'sa B, Raghuveer CV, Kamath A. Neovascularization of nucleus pulposus. A diagnostic feature of intervertebral disc prolapse. Spine (Phila Pa 1976). 1999;24(8):739-41.
39. Hukins D. Disc structure and function in Biology of the intervertebral disc. Ghosh P, editor: Boca Raton, FL: CRC Press; 1988.
40. Gruber HE, Hanley EN, Jr. Observations on morphologic changes in the aging and degenerating human disc: secondary collagen alterations. BMC Musculoskelet Disord. 2002;3:9.
41. Acaroglu ER, Iatridis JC, Setton LA, Foster RJ, Mow VC, Weidenbaum M. Degeneration and aging affect the tensile behavior of human lumbar anulus fibrosus. Spine. 1995;20(24):2690-701.
42. Liang C, Li H, Tao Y, Shen C, Li F, Shi Z, et al. New hypothesis of chronic back pain: low pH promotes nerve ingrowth into damaged intervertebral disks. Acta anaesthesiologica Scandinavica. 2013;57(3):271-7.
43. Specchia N, Pagnotta A, Toesca A, Greco F. Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine. Eur Spine J. 2002;11(2):145-51.
44. Thompson RE, Pearcy MJ, Downing KJ, Manthey BA, Parkinson IH, Fazzalari NL. Disc lesions and the mechanics of the intervertebral joint complex. Spine (Phila Pa 1976). 2000;25(23):3026-35.
45. Griffith JF, Wang YX, Antonio GE, Choi KC, Yu A, Ahuja AT, et al. Modified Pfirrmann grading system for lumbar intervertebral disc degeneration. Spine (Phila Pa 1976). 2007;32(24):E708-12.
46. 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):1873-8.
47. Quattrocchi CC, Alexandre AM, Della Pepa GM, Altavilla R, Zobel BB. Modic changes: anatomy, pathophysiology and clinical correlation. Acta neurochirurgica Supplement. 2011;108:49-53.
The following provides more detailed information about he process of disc degeneration. It is aimed at other health professionals, researchers and patients seeking to know more about the process of degeneration.
What Causes Disc Degeneration
Multiple cellular, biochemical and mechanical failures occur in the complex process of lumbar disc degeneration (LDD). The aetiology of disc aging and degeneration is complex and multifactorial, involving genetic, nutritional and mechanical factors(10), the result of which leads to changes in both the cellular and matrix components of the disc. An imbalance between extracellular matrix degradation and synthesis results in progressive failure of the disc with altered biomechanics at the affected spinal level. Disc degeneration is a progressive process, as the disc has limited ability for self-repair.
1. Mechanical Effects and disc injury
It seems logical that abnormal loading of the intervertebral disc would cause injury and subsequent degeneration. Disc degeneration appears more common in patients who perform repetitive physical work which constantly stresses the spine. Obesity has also been strongly linked to disc degeneration, with discs chronically overloaded by excessive body weight, and lacking support from weakened muscles secondary to sedentary lifestyles(11).
2. Genetics Effects
Numerous studies have confirmed a high familial predisposition to disc degeneration(12-16). Twin studies revealed an overall heritability of up to 75%(16-18), whilst Patel et al demonstrated a significantly elevated risk of developing degeneration in first (RR 4.15, P<0.001) and third-degree relatives (RR 1.46, P=0.027)(14). Genetic effects become more evident as age progresses and are affected by environmental influences, such as smoking and trauma(19). Gene polymorphisms involving genes encoding for aggrecan, collagens (I, II, IX), pro-inflammatory cytokine interleukin-1(IL-1), and matrix degrading enzymes, such as matrix-metalloproteinase-3 (MMP-3), have been implicated in the degenerative process(20-25).
3. Nutritional Influences on the disc
Inadequate supply of nutrients is an important factor contributing to LDD.
The intervertebral disc is essentially avascular, except for at the outer annular regions, and cells are dependent on diffusion of oxygen and metabolites across endplates and matrix tissue for adequate nutrition. The central nucleus pulposus cells are especially vulnerable to insult. A metabolite gradient exists throughout the disc with minimal nutrients (glucose, oxygen) and high levels of lactic acid present within central regions(26). With degeneration, this metabolite gradient is exaggerated influencing the degenerative process. When the tenuous nutrient supply is reduced, cell death and altered matrix production ensue, establishing a vicious cycle of cell compromise, matrix degradation and endplate changes, leading to further cell compromise, and subsequent advancement of degeneration.
Cigarette smoking, diabetes mellitus and atheroma can contribute to the development and progression of disc degeneration(27, 28).
What happens to discs during the process of aging and degeneration?
1. Cellular Changes
Approximately 1% of the intervertebral disc consistants of cartilage producing cells called chondrocytes. Overall there is a decrease in disc cell density and increased senescence of the cartilage cells(29, 30). Loss of appropriately functioning cells, due to both necrosis and apoptosis, is present in both aging biology and matrix production.
The loss of notochordal cells, which occurs with normal development in humans, and other chondrodystrophoid species, contributes to the degenerative process.
2. Disc Matrix Changes
Alterations in disc cell number and function, and cellular responses to nutritional deficiencies in turn leads to alterations in both the cartilaginous and proteoglycan matrix components of the disc. Proteoglycan (PG) loss occurs due to their decreased production by senescent disc cells and through increased expression of proteolytic enzymes(31-33). Loss of pivotal water-binding proteoglycan molecules leads to dehydration and collapse of the disc.
Changes in the collagenous matrix components also occur leading to fibrosis of the disc. Alterations in the constituents of the matrix and decreased water content results in decreased flexibility and altered load distribution leading to cleft and fissure formation in both the NP and AF(30, 34).
3. Endplate and Vertebral Body Changes
Bony endplate changes occur with thinning, calcification and alterations in vascularity, leading to a decreased ability for diffusion of nutrients and waste products of disc metabolism.
Change within the adjacent vertebral bodies also occurs, with evidence of sclerosis and bone micro-fracture(30). Osteophytes can also develop from the margins of the vertebral bodies and contribute to neural compression(35).
In addition, degenerative changes are also evident in the corresponding facet joints, suggesting that disc degeneration is the primary event leading to the clinical condition of degenerative spondylosis(36).
4. Neural and Vascular Changes
As disc degeneration progresses neo-vascularisation (blood vessel growth), with concurrent neo-innervation (nerve growth), can occur within the degenerative disc(5, 37, 38).
With the loss of the water binding PGs from the disc, its capacity to absorb and efficiently distribute weight axial and rotational loads is diminished, resulting in additional mechanical stresses leading to concentric and radiating tears that may in the disc(12, 35, 39-41). These structural events are considered to provoke the proliferation and migration of blood vessels and nerve fibres, normally confined to the periphery of the disc, to the deeper regions of the disc(5, 12). The establishment of these extended nerve fibers has been cited as a major cause of chronic lower back pain in degenerate discs(4, 5, 42).
In addition to the nociceptive neural mediated pain, local production of cytokines (IL-1, IL-6, TNF-α), growth factors and other immuno-modulatory pro-inflammatory peptides (leukotriene B4, prostaglandin E2) within the degenerative disc, can contribute to, and augment, discogenic pain(10, 43).
5. Mechanical Changes
The alterations in disc matrix which occurs with degeneration ultimately leads to abnormal biomechanics at the affected level(44). The inability of the disc to function as a normal intervertebral motion segment and load distributor has critical implications for accelerating degeneration at both the affected level and adjacent levels, as well as precipitating pain in abnormally loaded structures, such as facet joints, ligaments and paraspinal musculature.
6. Morphological Features of Disc Degeneration
Disc degeneration disrupts the normal architecture of the disc to varying degrees, the most severe of which leads to complete collapse of the disc with loss of distinction between annulus fibrosus and nucleus pulposus. Eventually ankylosis or auto-fusion of the spinal motion segment can occur.
7. Radiological Features of Disc Degeneration
Radiographic imaging plays a crucial role in the clinical assessment of back pain, disc degeneration and other spinal pathologies. Magnetic Resonance Imaging (MRI), with its ability to accurately demonstrate disc morphology and hydration state, is now the “gold standard” imaging modality used to assess disc disease with smaller roles for computed tomography (CT) and plain X-ray imaging(45). An understanding of the imaging characteristics is crucial as they are endpoints commonly employed by researchers to determine the efficacy of biological treatments.
- Loss of disc height
- Loss of high signal on T2-weighted imaging within the NP and inner AF (dehydration or dessication of the disc)
- Cleft formation and fissuring through the NP and AF
- Loss of demarcation between NP and the inner and outer AF(45, 46)
- Signal changes, termed Modic changes, within the adjacent vertebral bodies(47)
References
1. van Tulder MW, Assendelft WJ, Koes BW, Bouter LM. Spinal radiographic findings and nonspecific low back pain. A systematic review of observational studies. Spine (Phila Pa 1976). 1997;22(4):427-34.
2. de Schepper EI, Damen J, van Meurs JB, Ginai AZ, Popham M, Hofman A, et al. The association between lumbar disc degeneration and low back pain: the influence of age, gender, and individual radiographic features. Spine (Phila Pa 1976). 2010;35(5):531-6.
3. Takatalo J, Karppinen J, Niinimaki J, Taimela S, Nayha S, Mutanen P, et al. Does lumbar disc degeneration on magnetic resonance imaging associate with low back symptom severity in young Finnish adults? Spine. 2011;36(25):2180-9.
4. Luoma K, Riihimaki H, Luukkonen R, Raininko R, Viikari-Juntura E, Lamminen A. Low back pain in relation to lumbar disc degeneration. Spine. 2000;25(4):487-92.
5. Brisby H. Pathology and possible mechanisms of nervous system response to disc degeneration. The Journal of bone and joint surgery American volume. 2006;88 Suppl 2:68-71.
6. Deyo RA, Weinstein JN. Low back pain. The New England journal of medicine. 2001;344(5):363-70.
7. Andersson GB. Epidemiological features of chronic low-back pain. Lancet. 1999;354(9178):581-5.
8. Hicks GE, Morone N, Weiner DK. Degenerative lumbar disc and facet disease in older adults: prevalence and clinical correlates. Spine. 2009;34(12):1301-6.
9. Takatalo J, Karppinen J, Niinimaki J, Taimela S, Nayha S, Mutanen P, et al. Does lumbar disc degeneration on MRI associate with low back symptom severity in young Finnish adults? Spine (Phila Pa 1976). 2011.
10. Paesold G, Nerlich AG, Boos N. Biological treatment strategies for disc degeneration: potentials and shortcomings. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2007;16(4):447-68.
11. Shiri R, Karppinen J, Leino-Arjas P, Solovieva S, Viikari-Juntura E. The association between obesity and low back pain: a meta-analysis. American journal of epidemiology. 2010;171(2):135-54.
12. Melrose J, Smith SM, Little CB, Moore RJ, Vernon-Roberts B, Fraser RD. Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2008;17(9):1131-48.
13. Matsui H, Kanamori M, Ishihara H, Yudoh K, Naruse Y, Tsuji H. Familial predisposition for lumbar degenerative disc disease. A case-control study. Spine (Phila Pa 1976). 1998;23(9):1029-34.
14. Patel AA, Spiker WR, Daubs M, Brodke D, Cannon-Albright LA. Evidence for an inherited predisposition to lumbar disc disease. J Bone Joint Surg Am. 2011;93(3):225-9.
15. Livshits G, Cohen Z, Higla O, Yakovenko K. Familial history, age and smoking are important risk factors for disc degeneration disease in Arabic pedigrees. European journal of epidemiology. 2001;17(7):643-51.
16. Williams FM, Popham M, Sambrook PN, Jones AF, Spector TD, MacGregor AJ. Progression of lumbar disc degeneration over a decade: a heritability study. Ann Rheum Dis. 2011;70(7):1203-7.
17. MacGregor AJ, Andrew T, Sambrook PN, Spector TD. Structural, psychological, and genetic influences on low back and neck pain: a study of adult female twins. Arthritis and rheumatism. 2004;51(2):160-7.
18. Battie MC, Videman T, Levalahti E, Gill K, Kaprio J. Genetic and environmental effects on disc degeneration by phenotype and spinal level: a multivariate twin study. Spine (Phila Pa 1976). 2008;33(25):2801-8.
19. Uei H, Matsuzaki H, Oda H, Nakajima S, Tokuhashi Y, Esumi M. Gene expression changes in an early stage of intervertebral disc degeneration induced by passive cigarette smoking. Spine (Phila Pa 1976). 2006;31(5):510-4.
20. Solovieva S, Kouhia S, Leino-Arjas P, Ala-Kokko L, Luoma K, Raininko R, et al. Interleukin 1 polymorphisms and intervertebral disc degeneration. Epidemiology. 2004;15(5):626-33.
21. Solovieva S, Leino-Arjas P, Saarela J, Luoma K, Raininko R, Riihimaki H. Possible association of interleukin 1 gene locus polymorphisms with low back pain. Pain. 2004;109(1-2):8-19.
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