Pathophysiology of Spinal Pain

  • Annie W. Hsu
  • Steven P. CohenEmail author
  • Yian Chen


Disorders of the spine are highly prevalent throughout the world and pose an enormous socioeconomic burden, costing billions of dollars in care annually in the United States alone. Treatments must be tailored to the specific spinal pain syndrome and its pathophysiological basis. Disc herniation or stenotic lesions causing nerve root compression will produce different symptoms than a degenerative arthropathy. In this chapter, we discuss the epidemiology, underlying etiology, pathology, and risk factors for a variety of common spinal disorders, including disc herniation, discogenic pain, spinal stenosis, facet arthropathy, and sacroiliac joint (SIJ) pain. We also highlight the cellular and molecular basis of spine pain secondary to metastatic cancer or primary rheumatological disorders, such as ankylosing spondylitis. Overall, we provide an overview of the pathophysiology underlying common conditions that affect patients with spine pain, with the hope that a firm understanding of the molecular, cellular, and physiological changes may prompt more specific therapy.


Spine pain Facet arthropathy Discogenic pain Sacroiliac joint pain Disc herniation Spinal stenosis Radiculopathy Pathophysiology Cancer Inflammatory disease 


  1. 1.
    Manchikanti L, Singh V, Datta S, Cohen SP, Hirsch JA, American Society of Interventional Pain Physicians. Comprehensive review of epidemiology, scope, and impact of spinal pain. Pain Physician. 2009;12(4):E35–70. PubMed PMID: 19668291.PubMedGoogle Scholar
  2. 2.
    Martin BI, Turner JA, Mirza SK, Lee MJ, Comstock BA, Deyo RA. Trends in health care expenditures, utilization, and health status among US adults with spine problems, 1997–2006. Spine. 2009;34(19):2077–84. PubMed PMID: 19675510.PubMedGoogle Scholar
  3. 3.
    Mafi JN, McCarthy EP, Davis RB, Landon BE. Worsening trends in the management and treatment of back pain. JAMA Intern Med. 2013;173(17):1573–81. PubMed PMID: 23896698. Pubmed Central PMCID: 4381435.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Hart LG, Deyo RA, Cherkin DC. Physician office visits for low back pain. Frequency, clinical evaluation, and treatment patterns from a U.S. national survey. Spine. 1995;20(1):11–9. PubMed PMID: 7709270.PubMedGoogle Scholar
  5. 5.
    Deyo RA, Mirza SK, Martin BI. Back pain prevalence and visit rates: estimates from U.S. national surveys, 2002. Spine. 2006;31(23):2724–7. PubMed PMID: 17077742.PubMedGoogle Scholar
  6. 6.
    Freburger JK, Holmes GM, Agans RP, Jackman AM, Darter JD, Wallace AS, et al. The rising prevalence of chronic low back pain. Arch Intern Med. 2009;169(3):251–8. PubMed PMID: 19204216. Pubmed Central PMCID: 4339077.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Luo X, Pietrobon R, Sun SX, Liu GG, Hey L. Estimates and patterns of direct health care expenditures among individuals with back pain in the United States. Spine. 2004;29(1):79–86. PubMed PMID: 14699281.PubMedGoogle Scholar
  8. 8.
    Hoy D, Brooks P, Blyth F, Buchbinder R. The epidemiology of low back pain. Best Pract Res Clin Rheumatol. 2010;24(6):769–81. PubMed PMID: 21665125.PubMedGoogle Scholar
  9. 9.
    Manchikanti L, Singh V, Falco FJ, Benyamin RM, Hirsch JA. Epidemiology of low back pain in adults. Neuromodulation. 2014;17(Suppl 2):3–10. PubMed PMID: 25395111.PubMedGoogle Scholar
  10. 10.
    Hoogendoorn WE, van Poppel MN, Bongers PM, Koes BW, Bouter LM. Systematic review of psychosocial factors at work and private life as risk factors for back pain. Spine. 2000;25(16):2114–25. PubMed PMID: 10954644.PubMedGoogle Scholar
  11. 11.
    Linton SJ. Occupational psychological factors increase the risk for back pain: a systematic review. J Occup Rehabil. 2001;11(1):53–66. PubMed PMID: 11706777.PubMedGoogle Scholar
  12. 12.
    Schroeder GD, Guyre CA, Vaccaro AR. The epidemiology and pathophysiology of lumbar disc herniations. Semin Spine Surg. 2015;28:2–7.Google Scholar
  13. 13.
    Roberts S, Menage J, Urban JP. Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc. Spine. 1989;14(2):166–74. PubMed PMID: 2922637.PubMedGoogle Scholar
  14. 14.
    Fardon DF, Williams AL, Dohring EJ, Murtagh FR, Gabriel Rothman SL, Sze GK. Lumbar disc nomenclature: version 2.0: recommendations of the combined task forces of the North American Spine Society, the American Society of Spine Radiology and the American Society of Neuroradiology. Spine J. 2014;14(11):2525–45. PubMed PMID: 24768732.PubMedGoogle Scholar
  15. 15.
    Hammer C, Heller J, Kepler C. Epidemiology and pathophysiology of cervical disc herniation. Semin Spine Surg. 2016;28(2):64–7.Google Scholar
  16. 16.
    Ma D, Liang Y, Wang D, Liu Z, Zhang W, Ma T, et al. Trend of the incidence of lumbar disc herniation: decreasing with aging in the elderly. Clin Interv Aging. 2013;8:1047–50. PubMed PMID: 23966775. Pubmed Central PMCID: 3743527.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Weiler C, Lopez-Ramos M, Mayer HM, Korge A, Siepe CJ, Wuertz K, et al. Histological analysis of surgical lumbar intervertebral disc tissue provides evidence for an association between disc degeneration and increased body mass index. BMC Res Notes. 2011;4:497. PubMed PMID: 22087871. Pubmed Central PMCID: 3226673.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Longo UG, Denaro L, Spiezia F, Forriol F, Maffulli N, Denaro V. Symptomatic disc herniation and serum lipid levels. Eur Spine J. 2011;20(10):1658–62. PubMed PMID: 21387192. Pubmed Central PMCID: 3175866.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Gordon SJ, Yang KH, Mayer PJ, Mace AH Jr, Kish VL, Radin EL. Mechanism of disc rupture. A preliminary report. Spine. 1991;16(4):450–6. PubMed PMID: 2047918.PubMedGoogle Scholar
  20. 20.
    Marshall LW, McGill SM. The role of axial torque in disc herniation. Clin Biomech. 2010;25(1):6–9. PubMed PMID: 19815318.Google Scholar
  21. 21.
    Zhang YG, Sun Z, Zhang Z, Liu J, Guo X. Risk factors for lumbar intervertebral disc herniation in Chinese population: a case-control study. Spine. 2009;34(25):E918–22. PubMed PMID: 19940721.PubMedGoogle Scholar
  22. 22.
    Edelson JG, Nathan H. Stages in the natural history of the vertebral end-plates. Spine. 1988;13(1):21–6. PubMed PMID: 3381133.PubMedGoogle Scholar
  23. 23.
    Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG. Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine. 2002;27(23):2631–44. PubMed PMID: 12461389.PubMedGoogle Scholar
  24. 24.
    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):10–4. PubMed PMID: 16595436.PubMedGoogle Scholar
  25. 25.
    Goupille P, Mulleman D, Valat JP. Radiculopathy associated with disc herniation. Ann Rheum Dis. 2006;65(2):141–3. PubMed PMID: 16410526. Pubmed Central PMCID: 1798036.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Doita M, Kanatani T, Ozaki T, Matsui N, Kurosaka M, Yoshiya S. Influence of macrophage infiltration of herniated disc tissue on the production of matrix metalloproteinases leading to disc resorption. Spine. 2001;26(14):1522–7. PubMed PMID: 11462080.PubMedGoogle Scholar
  27. 27.
    Kawaguchi S, Yamashita T, Katahira G, Yokozawa H, Torigoe T, Sato N. Chemokine profile of herniated intervertebral discs infiltrated with monocytes and macrophages. Spine. 2002;27(14):1511–6. PubMed PMID: 12131709.PubMedGoogle Scholar
  28. 28.
    Yamashita M, Ohtori S, Koshi T, Inoue G, Yamauchi K, Suzuki M, et al. Tumor necrosis factor-alpha in the nucleus pulposus mediates radicular pain, but not increase of inflammatory peptide, associated with nerve damage in mice. Spine. 2008;33(17):1836–42. PubMed PMID: 18670336.PubMedGoogle Scholar
  29. 29.
    Genevay S, Finckh A, Payer M, Mezin F, Tessitore E, Gabay C, et al. Elevated levels of tumor necrosis factor-alpha in periradicular fat tissue in patients with radiculopathy from herniated disc. Spine. 2008;33(19):2041–6. PubMed PMID: 18758358.PubMedGoogle Scholar
  30. 30.
    Andrade P, Hoogland G, Teernstra OP, van Aalst J, van Maren E, Daemen MA, et al. Elevated levels of tumor necrosis factor-alpha and TNFR1 in recurrent herniated lumbar discs correlate with chronicity of postoperative sciatic pain. Spine J. 2016;16(2):243–51. PubMed PMID: 26523959. Epub 2015/11/03. eng.PubMedGoogle Scholar
  31. 31.
    el Barzouhi A, Vleggeert-Lankamp CL, Lycklama à Nijeholt GJ, Van der Kallen BF, van den Hout WB, Jacobs WC, et al. Magnetic resonance imaging in follow-up assessment of sciatica. N Engl J Med. 2013;368(11):999–1007. PubMed PMID: 23484826.PubMedGoogle Scholar
  32. 32.
    Schwarzer AC, Aprill CN, Derby R, Fortin J, Kine G, Bogduk N. The prevalence and clinical features of internal disc disruption in patients with chronic low back pain. Spine. 1995;20(17):1878–83. PubMed PMID: 8560335.PubMedGoogle Scholar
  33. 33.
    Raj PP. Intervertebral disc: anatomy-physiology-pathophysiology-treatment. Pain Pract. 2008;8(1):18–44. PubMed PMID: 18211591.PubMedGoogle Scholar
  34. 34.
    Marchand F, Ahmed AM. Investigation of the laminate structure of lumbar disc anulus fibrosus. Spine. 1990;15(5):402–10. PubMed PMID: 2363068.PubMedGoogle Scholar
  35. 35.
    Garcia-Cosamalon J, del Valle ME, Calavia MG, Garcia-Suarez O, Lopez-Muniz A, Otero J, et al. Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain? J Anat. 2010;217(1):1–15. PubMed PMID: 20456524. Pubmed Central PMCID: 2913007.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Ito K, Creemers L. Mechanisms of intervertebral disk degeneration/injury and pain: a review. Global Spine J. 2013;3(3):145–52. PubMed PMID: 24436865. Pubmed Central PMCID: 3854582.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Bogduk N. Degenerative joint disease of the spine. Radiol Clin N Am. 2012;50(4):613–28. PubMed PMID: 22643388.PubMedGoogle Scholar
  38. 38.
    Farfan HF, Cossette JW, Robertson GH, Wells RV, Kraus H. The effects of torsion on the lumbar intervertebral joints: the role of torsion in the production of disc degeneration. J Bone Joint Surg Am. 1970;52(3):468–97. PubMed PMID: 5425641.PubMedGoogle Scholar
  39. 39.
    Veres SP, Robertson PA, Broom ND. The influence of torsion on disc herniation when combined with flexion. Eur Spine J. 2010;19(9):1468–78. PubMed PMID: 20437184. Pubmed Central PMCID: 2989279.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y. The pathogenesis of discogenic low back pain. J Bone Joint Surg Br. 2005;87(1):62–7. PubMed PMID: 15686239.PubMedGoogle Scholar
  41. 41.
    Freemont AJ, Watkins A, Le Maitre C, Baird P, Jeziorska M, Knight MT, et al. Nerve growth factor expression and innervation of the painful intervertebral disc. J Pathol. 2002;197(3):286–92. PubMed PMID: 12115873.PubMedGoogle Scholar
  42. 42.
    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. 2005;30(1):44–53; discussion 4. PubMed PMID: 15626980.PubMedGoogle Scholar
  43. 43.
    Johnsson KE. Lumbar spinal stenosis. A retrospective study of 163 cases in southern Sweden. Acta Orthop Scand. 1995;66(5):403–5. PubMed PMID: 7484117.PubMedGoogle Scholar
  44. 44.
    Genevay S, Atlas SJ. Lumbar spinal stenosis. Best Pract Res Clin Rheumatol. 2010;24(2):253–65. PubMed PMID: 20227646. Pubmed Central PMCID: 2841052.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Siebert E, Pruss H, Klingebiel R, Failli V, Einhaupl KM, Schwab JM. Lumbar spinal stenosis: syndrome, diagnostics and treatment. Nat Rev Neurol. 2009;5(7):392–403. PubMed PMID: 19578346.PubMedGoogle Scholar
  46. 46.
    Yoshiiwa T, Miyazaki M, Notani N, Ishihara T, Kawano M, Tsumura H. Analysis of the relationship between ligamentum flavum thickening and lumbar segmental instability, disc degeneration, and facet joint osteoarthritis in lumbar spinal stenosis. Asian Spine J. 2016;10(6):1132–40. PubMed PMID: 27994791. Pubmed Central PMCID: 5165005.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Kosaka H, Sairyo K, Biyani A, Leaman D, Yeasting R, Higashino K, et al. Pathomechanism of loss of elasticity and hypertrophy of lumbar ligamentum flavum in elderly patients with lumbar spinal canal stenosis. Spine. 2007;32(25):2805–11. PubMed PMID: 18246001.PubMedGoogle Scholar
  48. 48.
    Sairyo K, Biyani A, Goel VK, Leaman DW, Booth R Jr, Thomas J, et al. Lumbar ligamentum flavum hypertrophy is due to accumulation of inflammation-related scar tissue. Spine. 2007;32(11):E340–7. PubMed PMID: 17495768.PubMedGoogle Scholar
  49. 49.
    Sairyo K, Biyani A, Goel V, Leaman D, Booth R Jr, Thomas J, et al. Pathomechanism of ligamentum flavum hypertrophy: a multidisciplinary investigation based on clinical, biomechanical, histologic, and biologic assessments. Spine. 2005;30(23):2649–56. PubMed PMID: 16319751.PubMedGoogle Scholar
  50. 50.
    Cui G, Watanabe K, Miyauchi Y, Hosogane N, Tsuji T, Ishii K, et al. Matrix metalloproteinase 13 in the ligamentum flavum from lumbar spinal canal stenosis patients with and without diabetes mellitus. J Orthop Sci. 2011;16(6):785–90. PubMed PMID: 21830104.PubMedGoogle Scholar
  51. 51.
    Lohr M, Hampl JA, Lee JY, Ernestus RI, Deckert M, Stenzel W. Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-beta expression. Acta Neurochir. 2011;153(1):134–41. PubMed PMID: 20960015.PubMedGoogle Scholar
  52. 52.
    Oh IS, Ha KY. Matrix metalloproteinase-3 on ligamentum flavum in degenerative lumbar spondylolisthesis. Spine. 2009;34(16):E552–7. PubMed PMID: 19770597.PubMedGoogle Scholar
  53. 53.
    Park JB, Kong CG, Suhl KH, Chang ED, Riew KD. The increased expression of matrix metalloproteinases associated with elastin degradation and fibrosis of the ligamentum flavum in patients with lumbar spinal stenosis. Clin Orthop Surg. 2009;1(2):81–9. PubMed PMID: 19885059. Pubmed Central PMCID: 2766760.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Park JB, Lee JK, Park SJ, Riew KD. Hypertrophy of ligamentum flavum in lumbar spinal stenosis associated with increased proteinase inhibitor concentration. J Bone Joint Surg Am. 2005;87(12):2750–7. PubMed PMID: 16322626.PubMedGoogle Scholar
  55. 55.
    Shafaq N, Suzuki A, Terai H, Wakitani S, Nakamura H. Cellularity and cartilage matrix increased in hypertrophied ligamentum flavum: histopathological analysis focusing on the mechanical stress and bone morphogenetic protein signaling. J Spinal Disord Tech. 2012;25(2):107–15. PubMed PMID: 21430570.PubMedGoogle Scholar
  56. 56.
    Zhang Y, Chen J, Zhong ZM, Yang D, Zhu Q. Is platelet-derived growth factor-BB expression proportional to fibrosis in the hypertrophied lumber ligamentum flavum? Spine. 2010;35(25):E1479–86. PubMed PMID: 21102276.PubMedGoogle Scholar
  57. 57.
    Zhong ZM, Zha DS, Xiao WD, Wu SH, Wu Q, Zhang Y, et al. Hypertrophy of ligamentum flavum in lumbar spine stenosis associated with the increased expression of connective tissue growth factor. J Orthop Res. 2011;29(10):1592–7. PubMed PMID: 21484860.PubMedGoogle Scholar
  58. 58.
    Nadeau M, Rosas-Arellano MP, Gurr KR, Bailey SI, Taylor DC, Grewal R, et al. The reliability of differentiating neurogenic claudication from vascular claudication based on symptomatic presentation. Can J Surg. 2013;56(6):372–7. PubMed PMID: 24284143. Pubmed Central PMCID: 3859778.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Takahashi K, Kagechika K, Takino T, Matsui T, Miyazaki T, Shima I. Changes in epidural pressure during walking in patients with lumbar spinal stenosis. Spine. 1995;20(24):2746–9. PubMed PMID: 8747254.PubMedGoogle Scholar
  60. 60.
    Ooi Y, Mita F, Satoh Y. Myeloscopic study on lumbar spinal canal stenosis with special reference to intermittent claudication. Spine. 1990;15(6):544–9. PubMed PMID: 2402694.PubMedGoogle Scholar
  61. 61.
    Porter RW. Spinal stenosis and neurogenic claudication. Spine. 1996;21(17):2046–52. PubMed PMID: 8883210.PubMedGoogle Scholar
  62. 62.
    Yazaki S, Muramatsu T, Yoneda M, Fujita K. Venous pressure in the vertebral venous plexus and its role in cauda equina claudication. Nihon Seikeigeka Gakkai Zasshi. 1988;62(8):733–45. PubMed PMID: 3235893.PubMedGoogle Scholar
  63. 63.
    Hata M, Kawahara N, Tomita K. Influence of ligation of the internal iliac veins on the venous plexuses around the sacrum. J Orthop Sci. 1998;3(5):264–71. PubMed PMID: 9732561.PubMedGoogle Scholar
  64. 64.
    Ikawa M, Atsuta Y, Tsunekawa H. Ectopic firing due to artificial venous stasis in rat lumbar spinal canal stenosis model: a possible pathogenesis of neurogenic intermittent claudication. Spine. 2005;30(21):2393–7. PubMed PMID: 16261115.PubMedGoogle Scholar
  65. 65.
    Kobayashi S, Yoshizawa H, Yamada S. Pathology of lumbar nerve root compression. Part 1: Intraradicular inflammatory changes induced by mechanical compression. J Orthop Res. 2004;22(1):170–9. PubMed PMID: 14656677.PubMedGoogle Scholar
  66. 66.
    Cohen SP, Raja SN. Pathogenesis, diagnosis, and treatment of lumbar zygapophysial (facet) joint pain. Anesthesiology. 2007;106(3):591–614. PubMed PMID: 17325518.Google Scholar
  67. 67.
    Yang KH, King AI. Mechanism of facet load transmission as a hypothesis for low-back pain. Spine. 1984;9(6):557–65. PubMed PMID: 6238423.PubMedGoogle Scholar
  68. 68.
    Glover JR. Arthrography of the joints of the lumbar vertebral arches. Orthop Clin North Am. 1977;8(1):37–42. PubMed PMID: 854275.PubMedGoogle Scholar
  69. 69.
    Bogduk N. Clinical anatomy of the lumbar spine and sacrum. Edinburgh: Churchill Livingstone; 1997. p. 127–44.Google Scholar
  70. 70.
    Jerosch J, Castro WH, Liljenqvist U. Percutaneous facet coagulation: indication, technique, results, and complications. Neurosurg Clin N Am. 1996;7(1):119–34. PubMed PMID: 8835152.PubMedGoogle Scholar
  71. 71.
    Paris SV. Anatomy as related to function and pain. Orthop Clin N Am. 1983;14(3):475–89. PubMed PMID: 6223256.Google Scholar
  72. 72.
    Pedersen HE, Blunck CF, Gardner E. The anatomy of lumbosacral posterior rami and meningeal branches of spinal nerve (sinu-vertebral nerves); with an experimental study of their functions. J Bone Joint Surg Am. 1956;38-A(2):377–91. PubMed PMID: 13319400.PubMedGoogle Scholar
  73. 73.
    Suseki K, Takahashi Y, Takahashi K, Chiba T, Tanaka K, Morinaga T, et al. Innervation of the lumbar facet joints: origins and functions. Spine. 1997;22(5):477–85. PubMed PMID: 9076878.PubMedGoogle Scholar
  74. 74.
    Kallakuri S, Singh A, Chen C, Cavanaugh JM. Demonstration of substance P, calcitonin gene-related peptide, and protein gene product 9.5 containing nerve fibers in human cervical facet joint capsules. Spine. 2004;29(11):1182–6. PubMed PMID: 15167655.PubMedGoogle Scholar
  75. 75.
    Cavanaugh JM, Lu Y, Chen C, Kallakuri S. Pain generation in lumbar and cervical facet joints. J Bone Joint Surg Am. 2006;88(Suppl 2):63–7. PubMed PMID: 16595446.PubMedGoogle Scholar
  76. 76.
    Beaman DN, Graziano GP, Glover RA, Wojtys EM, Chang V. Substance P innervation of lumbar spine facet joints. Spine. 1993;18(8):1044–9. PubMed PMID: 7690159.PubMedGoogle Scholar
  77. 77.
    Odonkor CA, Chen Y, Adekoya P, Marascalchi BJ, Chaudhry-Richter H, Tang T, et al. Inciting events associated with lumbar facet joint pain. Anesth Analg. 2018;126:280–8. PubMed PMID: 28704245.PubMedGoogle Scholar
  78. 78.
    Ianuzzi A, Little JS, Chiu JB, Baitner A, Kawchuk G, Khalsa PS. Human lumbar facet joint capsule strains: I. During physiological motions. Spine J. 2004;4(2):141–52. PubMed PMID: 15016391.PubMedGoogle Scholar
  79. 79.
    Boszczyk BM, Boszczyk AA, Korge A, Grillhosl A, Boos WD, Putz R, et al. Immunohistochemical analysis of the extracellular matrix in the posterior capsule of the zygapophysial joints in patients with degenerative L4-5 motion segment instability. J Neurosurg. 2003;99(1 Suppl):27–33. PubMed PMID: 12859055.Google Scholar
  80. 80.
    Dory MA. Arthrography of the lumbar facet joints. Radiology. 1981;140(1):23–7. PubMed PMID: 6454162.PubMedGoogle Scholar
  81. 81.
    Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288(5472):1765–9. PubMed PMID: 10846153.PubMedGoogle Scholar
  82. 82.
    Ozaktay AC, Cavanaugh JM, Blagoev DC, Getchell TV, King AI. Effects of a carrageenan-induced inflammation in rabbit lumbar facet joint capsule and adjacent tissues. Neurosci Res. 1994;20(4):355–64. PubMed PMID: 7870388.PubMedGoogle Scholar
  83. 83.
    Ozaktay AC, Cavanaugh JM, Blagoev DC, King AI. Phospholipase A2-induced electrophysiologic and histologic changes in rabbit dorsal lumbar spine tissues. Spine. 1995;20(24):2659–68. PubMed PMID: 8747244.PubMedGoogle Scholar
  84. 84.
    Yamashita T, Cavanaugh JM, Ozaktay AC, Avramov AI, Getchell TV, King AI. Effect of substance P on mechanosensitive units of tissues around and in the lumbar facet joint. J Orthop Res. 1993;11(2):205–14. PubMed PMID: 7683334.PubMedGoogle Scholar
  85. 85.
    Cavanaugh JM, Ozaktay AC, Yamashita T, Avramov A, Getchell TV, King AI. Mechanisms of low back pain: a neurophysiologic and neuroanatomic study. Clin Orthop Relat Res. 1997;335:166–80. PubMed PMID: 9020216.Google Scholar
  86. 86.
    Oudenhoven RC. Lumbar monoradiculopathy due to unilateral facet hypertrophy. Neurosurgery. 1982;11(5):726–7. PubMed PMID: 7155342.PubMedGoogle Scholar
  87. 87.
    Wilde GP, Szypryt EP, Mulholland RC. Unilateral lumbar facet joint hypertrophy causing nerve root irritation. Ann R Coll Surg Engl. 1988;70(5):307–10. PubMed PMID: 3190129. Pubmed Central PMCID: 2498839.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Maigne JY, Maigne R, Guerin-Surville H. The lumbar mamillo-accessory foramen: a study of 203 lumbosacral spines. Surg Radiol Anat. 1991;13(1):29–32. PubMed PMID: 1905063.PubMedGoogle Scholar
  89. 89.
    Kang YM, Choi WS, Pickar JG. Electrophysiologic evidence for an intersegmental reflex pathway between lumbar paraspinal tissues. Spine. 2002;27(3):E56–63. PubMed PMID: 11805709.PubMedGoogle Scholar
  90. 90.
    Indahl A, Kaigle A, Reikeras O, Holm S. Electromyographic response of the porcine multifidus musculature after nerve stimulation. Spine. 1995;20(24):2652–8. PubMed PMID: 8747243.PubMedGoogle Scholar
  91. 91.
    Bernard TN Jr, Kirkaldy-Willis WH. Recognizing specific characteristics of nonspecific low back pain. Clin Orthop Relat Res. 1987;217:266–80. PubMed PMID: 2951048.Google Scholar
  92. 92.
    Schwarzer AC, Aprill CN, Bogduk N. The sacroiliac joint in chronic low back pain. Spine. 1995;20(1):31–7. PubMed PMID: 7709277.PubMedGoogle Scholar
  93. 93.
    Maigne JY, Aivaliklis A, Pfefer F. Results of sacroiliac joint double block and value of sacroiliac pain provocation tests in 54 patients with low back pain. Spine. 1996;21(16):1889–92. PubMed PMID: 8875721.PubMedGoogle Scholar
  94. 94.
    Bowen V, Cassidy JD. Macroscopic and microscopic anatomy of the sacroiliac joint from embryonic life until the eighth decade. Spine. 1981;6(6):620–8. PubMed PMID: 7336283.PubMedGoogle Scholar
  95. 95.
    Slipman CW, Whyte WS 2nd, Chow DW, Chou L, Lenrow D, Ellen M. Sacroiliac joint syndrome. Pain Physician. 2001;4(2):143–52. PubMed PMID: 16902687.PubMedGoogle Scholar
  96. 96.
    Vleeming A, Pool-Goudzwaard AL, Stoeckart R, van Wingerden JP, Snijders CJ. The posterior layer of the thoracolumbar fascia. Its function in load transfer from spine to legs. Spine. 1995;20(7):753–8. PubMed PMID: 7701385.PubMedGoogle Scholar
  97. 97.
    Cohen SP, Chen Y, Neufeld NJ. Sacroiliac joint pain: a comprehensive review of epidemiology, diagnosis and treatment. Expert Rev Neurother. 2013;13(1):99–116. PubMed PMID: 23253394.PubMedGoogle Scholar
  98. 98.
    McGrath MC, Zhang M. Lateral branches of dorsal sacral nerve plexus and the long posterior sacroiliac ligament. Surg Radiol Anat. 2005;27(4):327–30. PubMed PMID: 16237486.PubMedGoogle Scholar
  99. 99.
    Forst SL, Wheeler MT, Fortin JD, Vilensky JA. The sacroiliac joint: anatomy, physiology and clinical significance. Pain Physician. 2006;9(1):61–7. PubMed PMID: 16700283.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Nakagawa T. Study on the distribution of nerve filaments over the iliosacral joint and its adjacent region in the Japanese. Nihon Seikeigeka Gakkai zasshi. 1966;40(4):419–30. PubMed PMID: 6010341.PubMedGoogle Scholar
  101. 101.
    Fortin JD, Vilensky JA, Merkel GJ. Can the sacroiliac joint cause sciatica? Pain Physician. 2003;6(3):269–71. PubMed PMID: 16880870.PubMedGoogle Scholar
  102. 102.
    Sakamoto N, Yamashita T, Takebayashi T, Sekine M, Ishii S. An electrophysiologic study of mechanoreceptors in the sacroiliac joint and adjacent tissues. Spine. 2001;26(20):E468–71. PubMed PMID: 11598526.PubMedGoogle Scholar
  103. 103.
    Vilensky JA, O’Connor BL, Fortin JD, Merkel GJ, Jimenez AM, Scofield BA, et al. Histologic analysis of neural elements in the human sacroiliac joint. Spine. 2002;27(11):1202–7. PubMed PMID: 12045518.PubMedGoogle Scholar
  104. 104.
    Szadek KM, Hoogland PV, Zuurmond WW, De Lange JJ, Perez RS. Possible nociceptive structures in the sacroiliac joint cartilage: an immunohistochemical study. Clin Anat. 2010;23(2):192–8. PubMed PMID: 20014392.PubMedGoogle Scholar
  105. 105.
    Fortin JD, Washington WJ, Falco FJ. Three pathways between the sacroiliac joint and neural structures. AJNR Am J Neuroradiol. 1999;20(8):1429–34. PubMed PMID: 10512224.PubMedGoogle Scholar
  106. 106.
    Cohen SP. Sacroiliac joint pain: a comprehensive review of anatomy, diagnosis, and treatment. Anesth Analg. 2005;101(5):1440–53. PubMed PMID: 16244008.PubMedGoogle Scholar
  107. 107.
    Winter RB, Pinto WC. Pelvic obliquity. Its causes and its treatment. Spine. 1986;11(3):225–34. PubMed PMID: 3715623.PubMedGoogle Scholar
  108. 108.
    Schuit D, McPoil TG, Mulesa P. Incidence of sacroiliac joint malalignment in leg length discrepancies. J Am Podiatr Med Assoc. 1989;79(8):380–3. PubMed PMID: 2810074.PubMedGoogle Scholar
  109. 109.
    Kiapour A, Abdelgawad AA, Goel VK, Souccar A, Terai T, Ebraheim NA. Relationship between limb length discrepancy and load distribution across the sacroiliac joint--a finite element study. J Orthop Res. 2012;30(10):1577–80. PubMed PMID: 22488899.PubMedGoogle Scholar
  110. 110.
    Herzog W, Conway PJ. Gait analysis of sacroiliac joint patients. J Manip Physiol Ther. 1994;17(2):124–7. PubMed PMID: 8169541.Google Scholar
  111. 111.
    Marymont JV, Lynch MA, Henning CE. Exercise-related stress reaction of the sacroiliac joint: an unusual cause of low back pain in athletes. Am J Sports Med. 1986;14(4):320–3. PubMed PMID: 2942046.PubMedGoogle Scholar
  112. 112.
    Ebraheim NA, Elgafy H, Semaan HB. Computed tomographic findings in patients with persistent sacroiliac pain after posterior iliac graft harvesting. Spine. 2000;25(16):2047–51. PubMed PMID: 10954635.PubMedGoogle Scholar
  113. 113.
    Frymoyer JW, Hanley E, Howe J, Kuhlmann D, Matteri R. Disc excision and spine fusion in the management of lumbar disc disease. A minimum ten-year followup. Spine. 1978;3(1):1–6. PubMed PMID: 644389.PubMedGoogle Scholar
  114. 114.
    Katz V, Schofferman J, Reynolds J. The sacroiliac joint: a potential cause of pain after lumbar fusion to the sacrum. J Spinal Disord Tech. 2003;16(1):96–9. PubMed PMID: 12571491.PubMedGoogle Scholar
  115. 115.
    Unoki E, Abe E, Murai H, Kobayashi T, Abe T. Fusion of multiple segments can increase the incidence of sacroiliac joint pain after lumbar or lumbosacral fusion. Spine. 2016;41(12):999–1005. PubMed PMID: 26689576.PubMedGoogle Scholar
  116. 116.
    Berg G, Hammar M, Moller-Nielsen J, Linden U, Thorblad J. Low back pain during pregnancy. Obstet Gynecol. 1988;71(1):71–5. PubMed PMID: 2962023.PubMedGoogle Scholar
  117. 117.
    Eshed I, Miloh-Raz H, Dulitzki M, Lidar Z, Aharoni D, Liberman B, et al. Peripartum changes of the sacroiliac joints on MRI: increasing mechanical load correlating with signs of edema and inflammation kindling spondyloarthropathy in the genetically prone. Clin Rheumatol. 2015;34(8):1419–26. PubMed PMID: 26006255.PubMedGoogle Scholar
  118. 118.
    Chou LH, Slipman CW, Bhagia SM, Tsaur L, Bhat AL, Isaac Z, et al. Inciting events initiating injection-proven sacroiliac joint syndrome. Pain Med. 2004;5(1):26–32. PubMed PMID: 14996234.PubMedGoogle Scholar
  119. 119.
    Vleeming A, Van Wingerden JP, Dijkstra PF, Stoeckart R, Snijders CJ, Stijnen T. Mobility in the sacroiliac joints in the elderly: a kinematic and radiological study. Clin Biomech (Bristol, Avon). 1992;7(3):170–6. PubMed PMID: 23915725.Google Scholar
  120. 120.
    Fortin JD. Sacroiliac joint dysfunction: a new perspective. J Back Musculoskelet Rehabil. 1993;3(3):31–43. PubMed PMID: 24573095.PubMedGoogle Scholar
  121. 121.
    Alderink GJ. The sacroiliac joint: review of anatomy, mechanics, and function. J Orthop Sports Physical Ther. 1991;13(2):71–84. PubMed PMID: 18796854. Epub 1991/01/01. eng.Google Scholar
  122. 122.
    Tam LS, Gu J, Yu D. Pathogenesis of ankylosing spondylitis. Nat Rev Rheumatol. 2010;6(7):399–405. PubMed PMID: 20517295.PubMedGoogle Scholar
  123. 123.
    Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med. 2016;374(26):2563–74. PubMed PMID: 27355535.PubMedGoogle Scholar
  124. 124.
    Bidad K, Gracey E, Hemington KS, Mapplebeck JCS, Davis KD, Inman RD. Pain in ankylosing spondylitis: a neuro-immune collaboration. Nat Rev Rheumatol. 2017;13(7):410–20. PubMed PMID: 28615730.PubMedGoogle Scholar
  125. 125.
    Wu Q, Inman RD, Davis KD. Neuropathic pain in ankylosing spondylitis: a psychophysics and brain imaging study. Arthritis Rheum. 2013;65(6):1494–503. PubMed PMID: 23460087.PubMedGoogle Scholar
  126. 126.
    Lories RJ, Haroon N. Bone formation in axial spondyloarthritis. Best Pract Res Clin Rheumatol. 2014;28(5):765–77. PubMed PMID: 25488783.PubMedGoogle Scholar
  127. 127.
    Bleil J, Maier R, Hempfing A, Schlichting U, Appel H, Sieper J, et al. Histomorphologic and histomorphometric characteristics of zygapophyseal joint remodeling in ankylosing spondylitis. Arthritis Rheumatol. 2014;66(7):1745–54. PubMed PMID: 24574301.PubMedGoogle Scholar
  128. 128.
    Bartels RH, van der Linden YM, van der Graaf WT. Spinal extradural metastasis: review of current treatment options. CA Cancer J Clin. 2008;58(4):245–59. PubMed PMID: 18354080.PubMedGoogle Scholar
  129. 129.
    Kerba M, Wu JS, Duan Q, Hagen NA, Bennett MI. Neuropathic pain features in patients with bone metastases referred for palliative radiotherapy. J Clin Oncol. 2010;28(33):4892–7. PubMed PMID: 20921451.PubMedGoogle Scholar
  130. 130.
    Falk S, Dickenson AH. Pain and nociception: mechanisms of cancer-induced bone pain. J Clin Oncol. 2014;32(16):1647–54. PubMed PMID: 24799469.PubMedGoogle Scholar
  131. 131.
    Honore P, Schwei J, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML, et al. Cellular and neurochemical remodeling of the spinal cord in bone cancer pain. Prog Brain Res. 2000;129:389–97. PubMed PMID: 11098706.PubMedGoogle Scholar
  132. 132.
    Yanagisawa Y, Furue H, Kawamata T, Uta D, Yamamoto J, Furuse S, et al. Bone cancer induces a unique central sensitization through synaptic changes in a wide area of the spinal cord. Mol Pain. 2010;6:38. PubMed PMID: 20602757. Pubmed Central PMCID: 3020802.PubMedPubMedCentralGoogle Scholar
  133. 133.
    Huang W, Han Z, Liu J, Yu L, Yu X. Risk factors for recurrent lumbar disc herniation: a systematic review and meta-analysis. Medicine. 2016;95(2):e2378. PubMed PMID: 26765413. Pubmed Central PMCID: 4718239.PubMedPubMedCentralGoogle Scholar
  134. 134.
    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;17(2):CD007431. PubMed PMID: 20166095.Google Scholar
  135. 135.
    Tarulli AW, Raynor EM. Lumbosacral radiculopathy. Neurol Clin. 2007;25(2):387–405. PubMed PMID: 17445735.PubMedGoogle Scholar
  136. 136.
    Katz JN, Dalgas M, Stucki G, Katz NP, Bayley J, Fossel AH, et al. Degenerative lumbar spinal stenosis. Diagnostic value of the history and physical examination. Arthritis Rheum. 1995;38(9):1236–41. PubMed PMID: 7575718.PubMedGoogle Scholar
  137. 137.
    Katz JN, Harris MB. Clinical practice. Lumbar spinal stenosis. N Engl J Med. 2008;358(8):818–25. PubMed PMID: 18287604.PubMedGoogle Scholar
  138. 138.
    Gellhorn AC, Katz JN, Suri P. Osteoarthritis of the spine: the facet joints. Nat Rev Rheumatol. 2013;9(4):216–24. PubMed PMID: 23147891. Pubmed Central PMCID: 4012322.PubMedGoogle Scholar
  139. 139.
    Donelson R, Aprill C, Medcalf R, Grant W. A prospective study of centralization of lumbar and referred pain. A predictor of symptomatic discs and anular competence. Spine. 1997;22(10):1115–22. PubMed PMID: 9160470.PubMedGoogle Scholar
  140. 140.
    Berthelot JM, Delecrin J, Maugars Y, Passuti N. Contribution of centralization phenomenon to the diagnosis, prognosis, and treatment of diskogenic low back pain. Joint Bone Spine. 2007;74(4):319–23. PubMed PMID: 17572129.PubMedGoogle Scholar
  141. 141.
    Zhang YG, Guo TM, Guo X, Wu SX. Clinical diagnosis for discogenic low back pain. Int J Biol Sci. 2009;5(7):647–58. PubMed PMID: 19847321. Pubmed Central PMCID: 2764347.PubMedPubMedCentralGoogle Scholar
  142. 142.
    Malanga GA, Cruz Colon EJ. Myofascial low back pain: a review. Phys Med Rehabil Clin N Am. 2010;21(4):711–24. PubMed PMID: 20977957.PubMedGoogle Scholar
  143. 143.
    Yap EC. Myofascial pain--an overview. Ann Acad Med Singap. 2007;36(1):43–8. PubMed PMID: 17285185.PubMedGoogle Scholar
  144. 144.
    Suri P, Rainville J, Katz JN, Jouve C, Hartigan C, Limke J, et al. The accuracy of the physical examination for the diagnosis of midlumbar and low lumbar nerve root impingement. Spine. 2011;36(1):63–73. PubMed PMID: 20543768. Pubmed Central PMCID: 2978791.PubMedPubMedCentralGoogle Scholar
  145. 145.
    Hooten WM, Cohen SP. Evaluation and treatment of low back pain: a clinically focused review for primary care specialists. Mayo Clin Proc. 2015;90(12):1699–718. PubMed PMID: 26653300.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Anesthesiology and Critical Care MedicineJohns Hopkins HospitalBaltimoreUSA
  2. 2.Departments of Anesthesiology and Critical Care Medicine, Neurology, and Physical Medicine and RehabilitationJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Walter Reed National Military Medical CenterBethesdaUSA
  4. 4.Departments of Anesthesiology and Physical Medicine and RehabilitationUniformed Services University of the Health SciencesBethesdaUSA

Personalised recommendations