Annulus Fissures Encourage Blood Vessel and Nerve Ingrowth into Degenerated Intervertebral Disks

Abstract

Introduction Discogenic back pain is closely associated with fissures in the annulus fibrosus,1,2 and with ingrowth of nerves and blood vessels.3 We test the hypothesis that annulus fissures encourage such ingrowth. Materials and Methods Three complementary studies were performed. Firstly, 15 cadaveric disks that contained an annulus fissure were subjected to 1 kN compression, while a miniature pressure transducer was pulled through the disk to obtain distributions of matrix compressive stress perpendicular to the fissure axis. Secondly, safranin O staining was used to evaluate focal loss of proteoglycans from within annulus fissures in 25 surgically removed disk samples. A novel image analysis method was used to quantify proteoglycan concentration along a line profile that was perpendicular to the fissure axis. Thirdly, in 21 elderly cadaveric disks, proteoglycan and water concentration were measured biochemically in disrupted regions of annulus containing one or more fissures, and in adjacent intact regions. The second experiment had good spatial resolution but was unable to quantify proteoglycan loss precisely, whereas the third experiment had poor spatial resolution but allowed precise quantification of proteoglycan loss. Results Reductions in compressive stress within annulus fissures averaged 36>46%, and were greater than average at the fissure axis. Stress reductions were greater in degenerated disks, and were inversely related to nucleus pressure (R2 = 0.47, p < 0.005). Safranin O stain intensity indicated that proteoglycan concentration was typically reduced by 40% at a distance of 600 µm from the fissure axis, and the width of the proteoglycan-depleted zone increased with age (R2 = 0.29, p = 0.006) and with general proteoglycan loss (R2 = 0.32, p < 0.005). Disrupted regions of annulus contained 36 to 54% less proteoglycans than adjacent intact regions from the same disks, although water content was reduced only slightly ( p > 0.05). Conclusion Annulus fissures provide a low-pressure microenvironment, especially if there is insufficient fluid pressure in the disk nucleus to tension the annulus and prevent fissures from “opening up.” A disk's collagen network is disrupted within an annulus fissure, and this disruption, combined with low pressure, permits local tissue swelling even though some of the proteoglycans are lost in the process. Blood vessels are attracted into this microenvironment by a combination of low pressure (which is less likely to collapse hollow blood vessels than a high pressure) and by a low concentration of proteoglycans, which are known to inhibit blood vessel4 and nerve5 ingrowth. Finally, nerve ingrowth into annulus fissures is facilitated by the presence of blood vessels, and by the low proteoglycan concentration. In this way, an annulus fissure in a degenerated intervertebral disk comprises a distinct microenvironment that is mechanically and chemically conducive to nerve and blood vessel ingrowth. This can explain the close association between annulus fissures and suspected discogenic back pain. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared Videman T, Nurminen M. The occurrence of anular tears and their relation to lifetime back pain history: a cadaveric study using barium sulfate discography. Spine 2004;29(23):2668–2676 Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y. The pathogenesis of discogenic low back pain. Journal of Bone and Joint Surgery British Volume 2005;87(1):62–67 Freemont AJ, Peacock TE, Goupille P, Hoyland JA, O'Brien J, Jayson MI. Nerve ingrowth into diseased intervertebral disk in chronic back pain. Lancet. 1997;350(9072):178–1781 Johnson WE, Caterson B, Eisenstein SM, Roberts S. Human intervertebral disk aggrecan inhibits endothelial cell adhesion and cell migration in vitro. Spine 2005;30(10):1139–1147 Johnson WE, Caterson B, Eisenstein SM, Hynds DL, Snow DM, Roberts S. Human intervertebral disk aggrecan inhibits nerve growth in vitro. Arthritis and Rheumatism 2002;46(10):2658–2664