Pathophysiology of low back pain


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Pathophysiology of low back pain

  1. 1. Dr. Sushil Paudel
  2. 2.  Low back pain is the most commonmusculoskeletal disorder in industrializedsocieties. AAOS, Dept of Research and Scientific Affairs Workers’ compensation statistics suggest thatdisability for back pain is increasing 14 timesthe population growth. Aronoff, 1991
  3. 3. Lumbar Spinal MRI (n = 131) n (%) of regionIntervertebral disc degeneration 116 (88.5)Intervertebral disc bulge or herniation 101 (77.1)Posterior joint degeneration 42 (32.1)Facet tropism 9 (7.2)Spondylolisthesis, grade I 6 (5.6)Congenital narrow central stenosis, L4 and L5 6 (5.4)Acquired central stenosis, L4 and L5 4 (3.1)Conjoined nerve root 2 (1.5)Transitional segmentation 2 (1.5)Uterine mass 2 (1.5)Neurofibroma 2 (1.5)Malignant alteration of bone marrow 1 (0.8)- Marchiori et al. 2002
  4. 4. The intervertebral discis comprised of: The nucleuspulposus The anulus fibrosus The vertebralendplates
  5. 5.  Disc- Derived From:◦ Notochord◦ Somatocoele Mesenchymal Cells Mesenchymal Cells◦ Dense Celled Zone – Forms the disc◦ Loose Celled Zone – Forms the vertebral bodies◦ Outer Zone – forms fibroblasts Cotton et al. 1994 Mirza and White, 1995
  6. 6.  10 Weeks◦ Notochord cells disappear from vertebral body 11-20 Weeks◦ Nucleus forms from expansion of the notochord◦ Annular formation begins After 20 Weeks◦ Notochord cells decrease◦ Collagen fibers form in the annulus Cotton et al. 1994 Mirza and White, 1995
  7. 7.  Consists of 15 to 25 layers of fiber bundles Layers are 0.14 to 0.52 mm thick Average interbundle space is 0.22 mm wideand filled with gelatinous material Structure of the anulus is irregular◦ 40% of the layers are incomplete in any 20 degreecircumferential sector of the disc◦ Irregularities are most frequent in the posterolateralregion of the anulus Marchand and Ahmed 1990
  8. 8.  Consists of a clear gelatinous substance Makes up 50% of the disc Moves within the disc with changes in posture Communicates with the epidural space andsurrounding neural structures Beattie et al. 1994 MacMillan et al. 1991
  9. 9.  MacMillam et al analyzed 105 discs withmethylene blue dye injected in the nucleus◦ 14% showed leaks◦ 93% of the leaks were in the posterolateral region◦ Injected dye showed contact with the adjacent nerveroot in 27% of the leaks MacMillan et al. 1991
  10. 10.  The end plateconsists of a thinflat layer of hyalinecartilage. Each EP is composedof parallel lamellaeof chondrocytes andcollagen fibers The EP contributesto resilience of themotion segment Ghosh, 1990
  11. 11.  Located cephalad in the foramen and bathed inCSF With SLR, the lumbar nerve roots move 0.5-5 mmand sustain 2-4% strain. – Smith et al. 1993 A more transverse course of the nerve root maybe associated with an increased risk of sciatica Sato and Kikuchi, 1993 Conjoined nerve roots:◦ 2-4% of patients undergoing imaging studies - Okuwaki etal. 1991◦ 14% of anatomic studies◦ May be associated with developmental anomalies andincreased risk of disc herniation - Gomez et al. 1993
  12. 12.  Lumbar region◦ Loosely connected in upper levels◦ Smaller diameter at lower levels Morphologically associated with herniation◦ Intact PLL - central herniation in upper levels◦ Ruptured PLL - posterolateral extrusion in lowerlevels Ohshima et al. 1993
  13. 13.  Normalintervertebralforamen is ovalshaped With discdegeneration, foramen assumes anauricular shape Stephens et al. 1991
  14. 14.  Provide torsional rigidityand provide structuralsupport in axial loading Zimmerman et al. 1992 Posterior elementsrestrict the disc to 80% ofits full range of flexion Degeneration and arthritisof the facet joint is linkedwith decreased discheight as a result of DDD. Adams et al. 1994
  15. 15.  The normal disc is avascular Segmental blood vessels contribute to thecapillary bed surrounding the anulus Stairmand et al. 1991 Blood vessels penetrate the subchondral boneof the vertebral body and calcified region ofthe hyaline cartilage end plate Invasion of blood vessels from the exterior isseen in people age >50 years Yasuma et al. 1993
  16. 16. - Modified from Postacchini and Rausching, Anatomy, 1999
  17. 17.  Anterior annulus isinnervated by nervesderived from the ventralrami and gray ramuscommunicans Yamashita et al. 1993 The posterior annulus isinnervated by thesinuvertebral nerve –McCarthy et al. 1991 No nerve fibers orneuropeptides have beenidentified in normalnucleus pulposus Ashton et al. 1994- Modified from Postacchini andRausching, Anatomy, 1999
  18. 18. - Modified from Postacchini and Rausching, Anatomy, 1999
  19. 19.  Nerve endings in the outer half of the anulus innormal and degenerated discs – Yoshizawa et al. 1980 Nerve fibers may extend 3mm into the anulus ofa normal disc Nerve endings in abnormal discs may reach thenucleus Ashton et al. 1994
  20. 20. NP AFWaterYoung Disc 85-90 % 78%Older Disc 70% 70%Solids 10-20% 30-40%Proteoglycans 65% 20%Collagen 20-30% 50-60%Elastin ~1% ~1%- Gumina and Postacchini, 1998, Mirza and White, 1995
  21. 21.  Healthy Disc◦ Average daily variation of 1.2 mm Degenerated Disc◦ Average daily variation of 2.1 mm Diurnal Variation◦ 13 to 21 mm variation in healthy 22-year olds◦ Prolonged bed rest is associated with 22% expansionof the disc◦ Increased disc space may increase diffusion distances Paajanen et al. 1994 LaBlanc et al. 1994
  22. 22.  Intradiscal pressure is lowest in supineposition Nachemson, 1960 Intradiscal pressure rises in the sitting,leaning forward position 65% of height loss occurs in the first 6 minafter a 10 kg weight is lifted Krag et al. 1990
  23. 23.  The disc is largely avascular Metabolism is mainly anaerobic Nutrients enter by diffusion via two routes Diffusion through the end plates◦ Perianular◦ Diffusion distance may be as large as 8 mm Load dependant◦ Metabolism in bovine discs was highest with 5 to 10kg loads – Ohshima et al. 1995◦ A physiologic level (0.33 MPa) of hydrostatic pressureacts in an anabolic fashion, stimulating proteoglycansynthesis – Handa et al. 1997
  24. 24.  Maximum cell density of the disc isdetermined by nutrient supply Oxygen and glucose levels within the discmay fall to very low levels Stairmand et al. 1991 Oxygen◦ At the center of the disc O2 is 1/20 to 1/50 of thatat the edge of the disc Lactate◦ At the center of the disc is 8 to 10 times the plasmaconcentration Holm et al. 1981
  25. 25. Cell Density (x 10-3)/mm3Age 15 years 18 years 56 years AverageCartilage end plate 12.6 15.4 17.1 15.0Anulus fibrosus 6.9 8.4 11.6 9.0Nucleus pulposus 3.3 4.3 4.7 4.0- Maroudas et al. 1975
  26. 26.  Anular injury can initiate progressivedegenerative changes◦ Nucleus becomes small, fibrotic, and developsyellowish discoloration◦ Replacement of lamellae with granulation tissue◦ Lamellar structure was not restored in the area ofinjury 3 to 5 months following injury◦ Development of ventral osteophytes◦ Collagen synthesis and content increased, cross linksdecreased, water content decreased Kaapa et al. 1994 Osti et al. 1990
  27. 27. Degeneration at the L4-5 disc predicteddecreased loads on the facet joints, increasedintradiscal pressure (by 10%), and increaseddisc bulge at the L3-4 level in a finite elementmodel- Kim et al. 1991
  28. 28.  Intervertebral disc prolapse is peripheral inorigin with the anulus being the site of primarypathological change Gordon et al. 1991 Bending in addition to axial compression inpredisposing a disc to prolapse Adams, 1994 The normal disc is protected by the posteriorelements from overstretching, however notfrom fatigue failure Adams et al. 1994
  29. 29. Proteoglycan levels decrease with◦ Disc degeneration◦ Age◦ Altered loading◦ A pH decrease from 6.9-7.1 to less than 6.5 May be due to degeneration or smoking◦ NSAID use Yoo et al. 1992 Ohshima and Urban, 1992 Ohshima et al. 1995 (J Orthop Res)
  30. 30.  Many changes occur before maturity◦ Collagen in the nucleus increases in lumbar regions◦ Collagen in the anulus increases◦ Water content decreases◦ Chondroitin sulfate and polyanion concentrationsdecrease◦ Hyaluronic acid and keratan sulfate increase◦ Increase in elastin to proteoglycan ratio◦ Decrease in elastin to collagen ratio Scott et al. 1994
  31. 31. Aging leads to loss of anular integrity Bernick et al. 1991 In persons over 40 years of age◦ Breakdown of lamina and thickening of lamellar layers◦ Fraying, splitting, loss of collagen fibers◦ Spaces filled with proteoglycan◦ Deposition of chondroid material in the anulus◦ Amyloid deposition in the anulus◦ Circumferential and radial ruptures are noted Ito et al. 1991 Marchand and Ahmed 1990
  32. 32. Aging may lead to: Calcification and gradual replacement with bone Bernick et al. 1991 May become separated from subchondral boneand herniate with the anulus◦ In 51.1% of persons aged 77 years, end plate isseparated – Tanaka et al. 1993 Irregularities may become common◦ Bone marrow tissues may penetrate the endplate, triggering cytokine production leading to matrixdegradation Fujita et al. 1993
  33. 33. Aging may lead to: Increased contact forces over the facet jointsdue to loss of disc height Shirazie-Adl, 1992 Facet osteoarthritis may occur secondary tomechanical changes resulting from discdegeneration Butler et al. 1990
  34. 34.  Genetic factors have been linked to discdegeneration in identical twins. Sambrook et al. 1999 Battie et al. 1995 Harrington et al. 2001 analyzed fivefactors: height, weight, body mass index,disc endplate area, and disc endplate size. Only disc endplate shape had a strongassociation with disc herniationoccurrence Disc endplate area had a borderlineassociation with disc herniationoccurrence in men.
  35. 35.  Mechanical factors such as: small discs,a heavy torso, or small internal leversmay lead to high internal muscle forcesacting on the disc. Videmann, 2001 Collagen Expression◦ Defects in Collagen IX (CLO9A2), astructural element of the anulus fibrosus,nucleus pulposus, and the endplates, havebeen associated with dominantly inheritedlumbar disc disease. Paasilta et al. 2001 Annunen et al. 1999 Jones et al. 1998
  36. 36. Method of Lifting Relative RiskKnees bent and back straight 0.71Knees bent and back bent 2.02Knees straight and back bent 3.95Lifting starting and ending at floor level 1.84Lifting starting and ending at waist level 2.53Lifting started with arms extended 1.87Twisting while lifting 1.90Adapted from Mundt et al. 1993
  37. 37.  Smoking has been linked to disc degenerationin studies of identical twins. Lebeouf-Yde et al. 1998 Battie et al. 1991 Smoking – increases intradiscal lactate levels,decreases pH, and degrades hyaluronic acid. Hambly and Mooney, 1992 McDevitt et al. 1985 Holm and Nachemson 1988 Narrows the vascular lumen and reduces thenumber of vascular buds present in theendplate Iwahashi et al. 2002
  38. 38. Other Industrial WorkersBuilding WorkersDriversFarmersProfessional and white collar workersSuspected Herniation (or sciatica) Documented HerniationAdapted from Heliovaara, 1987
  39. 39. Stenosis of the ostia of the arteries supplyingthe disc has been correlated to degree of discdegeneration. Kauppila et al. 1994
  40. 40.  21.5% of herniated discs contain both nuclearand anular material 29% of herniated discs contain only anularmaterial Lebkowski and Dzieciol 2002 Most recurrent disc herniations andherniations with multiple extruded fragmentscontain portions of endplate Brock et al. 1992
  41. 41.  The prevalence of disc herniation is 1.6% inthe US, 2.2% in England, and 1.2% in Finland The prevalence of low back pain is 15-20% inthe US, 25-45% in European countries, with alife-time prevalence exceeding 70%
  42. 42.  Neovascularization was seen in 12.5% ofherniated discs in patients with less than 1month duration and in 82% of herniated discsin patients with symptoms greater than 6month duration. Chitkara, 1991 Neovascularization was seen in 91% ofherniated discs in patients with symptomduration ranging from 5 days to 2.5 years Sequestered herniations had greaterneovascularization than did protrusions Virri et al., 1996
  43. 43.  In 80% of degenerated discs, solitary freenerve fibers could be seen deeper than theouter third of the annulus In 20% of degenerated discs, free nervefibers were discernible in the periphery ofthe NP Coppes et al. 1997, COPPES et al. 1990 Freemont et al. 1997 Bogduk et al. 1981
  44. 44.  Neuropeptides involved in the transmission ofpain have been identified in the intervertebraldisc:◦ CGRP, VIP, and SP are present in the outer anulus ofdog discs Chemical events in the disc following injurymay sensitize the DRG and generate pain Weinstein et al. 1988
  45. 45.  Acute compression of the nerve root with discprotrusion is estimated to generate a contactpressure of ~ 400 mm Hg compression.Spencer et al. 1984 This compression may cause numbness,parasthesiae, and weakness but not pain.Rydevik et al. 1984, Garfin et al. 1991 5-10 mm Hg of pressure causes impairmentin blood flow 50-75 mm Hg of pressure causes increasedpermeability of blood vessels, edema,increased tissue pressure, altered local ionbalance, and altered impulse contractionOlmarker et al. 1989, Lind et al. 1993
  46. 46.  Compression of an inflamed nerve root maycause pain Proposed mechanisms of inflammation◦ Lowered pH◦ Breakdown products from nucleus◦ Proteoglycans from disc◦ Autoimmune reaction to exposed disc tissue Mirza and White, 1995
  47. 47.  Application of NP to the nerve root reducesblood flow in the DRG and causes vascularchanges and hypoxia. Causes hypersensitivity leading to anincreased spontaneous discharge rate. Excitation and mechanical hypersensitivitymay be induced without mechanicalcompression.- Takebayashi, et al. 2001
  48. 48. InflammatoryMediatorsNormal DegenerativeDiscGelatinase 1.05 5.76Caseinase (Stromelysin) 0.110 0.432Nitric Oxide (nmol/g) 51.33 132.21Interleukin -6 174 30401PG E2 (ng/ml) 1.71 20.85
  49. 49.  Nucleus pulposus-induced effects on the nerveroot seems to be mediated by disc cell-relatedcytokines, which in turn have a role inmediation of the immune response. Brisby et al. 2000
  50. 50. Proteoglycan SynthesisMatrix DegenerationDirect Stimulationand Sensitizationof DRG andSpinal Nerve RootNet Loss of ProteoglycanDisc DegenerationLOW BACK PAIN RADICULOPATHYCYTOKINESNITRIC OXIDEPGE2OTHER INFLAMMATORY AGENTSDirect Stimulationand Sensitizationof Nerve Endingsof the FunctionalSpine Unit- Kang et al. 1997
  51. 51. ◦ Involved in vasodilation, neurotransmission,cytotoxicity and gene regulation in several organsystems Hashizume et al. 1997◦ Involved in the inhibition of proteoglycan synthesis byIL-1 Kang et al. 1997◦ Synthesis may be stimulated by TNF- and othercytokines. Aoki et al. 2002
  52. 52. ◦ Include Collagenase-1 and -3 (MMP-1 and -13)and Gelatinase A and B (MMP-2 and –9)◦ Involved in the normal turnover and pathologicdegradation of extracellular matrix in connectivetissues Borden and Heller, 1997◦ Able to degrade all known matrix components,including collagen types I, II, and III, which makeup 80% of the disc collagen Roberts et al. 2000
  53. 53. ◦ PGE2 and IL-6 are present in large quantities in theherniated discs◦ Both are strongly stimulated by IL-1◦ In articular cartilage, IL-6 and PGE2 may bepossible intermediaries in the suppression ofproteoglycan synthesis Kang et al. 1996
  54. 54. Phospholipase A2◦ Lipolytic enzyme which hydrolyzescertain phospholipids and freefatty acids, generatingprostaglandins and othereicosanoids which are potentinflammatory mediators◦ Application onto nerve roots inrats resulted in demyelination inthe nerve fibers and increasedectopic discharges in response tomechanical stimuli. Chen et al. 1997
  55. 55.  PA2 activity is 20,000 to 100,000 fold morethan any other phospholipase activity PA2 extracted from the human lumbar dischas a powerful inflammatory effect in vivo Increased PA2 activity is seen in disc tissue◦ 50 times higher than in synovial tissue Saal et al. 1990
  56. 56.  The effect of tumor necrosis factor TNF- onthe nerve root was remarkably similar to theeffect of application of the nucleus pulposusitself, indicating that TNF- may be an “earlyplayer” in pathophysiologic reactionsresulting from nerve root injury. Aoki et al. 2002
  57. 57.  The left L5 nerve root and corresponding DRGwere examined with application of TNF- , aswell as on response to pinch and brushstimulation with and without application ofTNF- .◦ Spontaneous discharge of both wide dynamicrange and nociceptive specific neurons increasedsignificantly within 2 hours of application.◦ Within 2 hours of application, discharge from pinchstimulation became more intense and prolonged.◦ No change was observed between control andexperimental groups in response to brushstimulation. Onda, et al. 2002
  58. 58.  CT◦ Excellent imaging of bones, inadequate for nerve roots◦ Less sensitive than MRI for disc pathology MRI◦ Detailed imaging of discs and nerve roots◦ Detailed imaging of herniation Discography◦ Necessary for confirmation of the painful disc
  59. 59.  Discograms produce mechanical stimulus Injection may directly stimulate sensitizednerve fibers in the anulus Weinstein et al. 1988 False-positive rate has been reported as0% Gunzburg et al. 1992 Specificity has been reported as 31% Walsh et al. 1990 Sensitivity has been reported as 81-100% Nachemson, 1989
  60. 60.  Early degenerative disc disease may existbefore there is loss of disc height or signalintensity, therefore appearing normal on MRI Scheibler et al. 1991 Brightbill et al. 1994 MRI is less specific than discography indetecting disc pathology Gunzburg et al. 1992
  61. 61. Confirmation of the exactsymptomatic disc level(s):A recent study indicated that normal MRIand T2-weighted MRI with additional Gd-DTPA-enhanced images were superior atidentifying posterior annular tears,however could not replace discography interms of confirming the exact symptomaticdisc level(s). Yoshida et al. 2002
  62. 62.  The size of disc herniation in relation to thesize of the spinal canal has been reported toprovide the best correlation to clinical findings Sagittal plane ratio of disc herniation to canalsize has also been correlated to the degree ofsciatic pain. Thelander et al. 1994
  63. 63. Classification FindingsBulge Symmetric extension beyond boneProtrusion Asymmetric extension of anulusbeyond boneExtrusion Focal extension beyond anulusFree Fragment Herniated material dissociatedfrom the disc- Modified from Mirza and White, 1995
  64. 64. -Modified fromAdams, 2002
  65. 65. Grade Nucleus Anulus End Plate VertebralBodyI Bulging Discrete lamellae UniformthicknessRoundedmarginsII Fibrous changesperipherallyMucinous materialbetween lamellaeIrregularthicknessPointedmarginsIII Consolidatedfibrous changesLoss of anulardemarcationFocal defects ChondrophytesIV Horizontal cleftsin the nucleusFocal disruptions Fibrocartilage <2 mmosteophytesV Clefts extendinginto the anulusClefts throughanulusDiffusesclerosis>2 mmosteophytes- Modified from Thompson et al. 1990
  66. 66. The anterior portion of the sic is considerably larger than the posterior and the anterior annularlamellae have lost their curvature, whereas the posterior lamellae have an increased curvature.A portion of the NP is displaced dorsally with respect to the rest of the nucleus.- Modified from Postacchini and Rausching, Anatomy, 1999
  67. 67. The L4-L5 disc is decreased in height and a long radial cleft is visible (arrowhead). Thevertebral bodies are no longer covered by the cartilage EPs. The posterior AF bulges and is incontact with the ligamentum flavum (asterisk). The L5-S1 disc is almost completely resorbedand also demonstrates a radial fissure and bulging AF.- Modified from Postacchini and Rausching, Pathomorphology, 1999
  68. 68. Lateral sagittal section of a cadaver spine at L4-L5 level. The intervertebral disc, ofnormal height, shows fissures in the posterior AF reaching in proximity to the outermostlamellae. The annulus bulges into the vertebral canal and, in its caudal portion, theprominence has the appearance of a true herniation. Asterisk: ligamentum flavum locatedventrally to the facet joint.- Modified from Postacchini and Rausching, Pathomorphology, 1999
  69. 69. Combined stenosis of the spinal canal resulting from moderate constitutional narrowing of thecanal and thickening of the ligamenta flava (asterisk) associated with mild hypertrophy of thearticular processes.- Modified from Postacchini and Rausching, Pathomorphology, 1999