4 Pathophysiology and Operative Treatment of Discogenic Back Pain Abstract In order to adequately treat patients with chronic lower back pain, an understanding of the pathophysiology of back pain is paramount. Although further basic science and clinical research into this subject is necessary, inflammatory nerve-irritating substances released from the degenerate disc have recently been identified as playing a critical role. This chapter will discuss the anatomic architecture of the disc as well as the pathophysiology of disc degeneration leading to chronic back and/or leg pain. Keywords: degenerated disc, back pain, discogenic back pain, inflammatory mediators The intervertebral disc is an active organ in which the normal and pathologic anatomy are well known but the normal and pathologic physiology have been less clear. The flexible disc, interposed between each movable segment, permits cyclical motions required of all vertebrate animals in their various forms of locomotion. The disc is a high-pressure system composed primarily of absorbed water, an outer multilayered circumferential belt of strong, flexible but essentially inelastic collagen fibers, and an inner core of a hydrogel called the nucleus pulposus. The swelling of the contained hydrogel creates the high pressure that tightens the annular fibers and maintains disc height and resilience, very much as the air in a belted tire tightens its laminations. Degeneration of discs is a slow, complex process involving several mechanical and physiologic components. Discogenic pain arises from either component but is primarily due to altered chemistry. When this pain is severely disabling and unyielding, the preferred contemporary treatments are primarily surgical—namely, fusion or total disc replacement. The embryology, developmental anatomy, and physiology of the disc are complex.1,2,3,4,5,6,7,8 The annulus fibrosus of the disc has a mesenchymal embryologic origin as does muscle, bone, and connective tissue. The nucleus pulposus, however, develops from the notochord. The intervertebral discs allow for dynamic motion of the axial skeletal structure at each vertebral segment. The disc is composed primarily of absorbed water, a multilayered annular ring of flexible inelastic type 1 long collagen fibers (similar to those found in ligaments), and a gelatinous core.2,8,9 The annulus provides the means by which the disc attaches to vertebral bone. Annular collagen fibers are arranged in circumferential belts or laminations inserting strongly and tangentially in right- and left-handed angulated patches into each adjacent vertebral body2 ( Fig. 4.1 (a) Diagram of a multibelted radial tire showing circumferential, radial, and tangential fibers. This configuration provides maximum stability, but the fibers must be kept tight as a result of the high internal air pressure. With loss of internal pressure, the tire laminations bulge, debond, delaminate, and disintegrate. Between fiber layers is interposed a thin layer of flexible rubber. (The image is provided courtesy of Semperit Tire & Rubber Co.) (b) Diagram of an intervertebral disc showing the multilaminated annulus. Type 1 long collagen fibers firmly attach to adjacent vertebral bodies. The overlapping laminations, randomly constructed in right-hand and left-hand patches in a given layer, provide maximum stability of the segment in all degrees of freedom so long as the fibers are tightened by the internal swelling of the nucleus gel. This swelling of the gel is analogous to the air inside the tire. The internal nucleus pressure varies from approximately 2 to 10 atmospheres depending on the load, and is clearly far above normal arterial pressure, so there cannot be an intrinsic vascular supply within the normal annulus or nucleus.6,15,16 The lumbar discs are the largest avascular structures of the body. This semi-sealed disc chamber is anaerobic, with the oxygen saturation approximately 5%.6,15 Only the outer six annular layers have a direct arteriolar supply, along with a thin arteriolar supply lying outside of the end plate.17 Normally, small arterioles are always accompanied by small free nerve endings, or C-fibers, mediators of pain perception. These tiny nerves, 2 to 6 μm in diameter, are polymodal, responding to chemical, thermal, or mechanical stimuli17 ( The disc normally expands and contracts during the daily cycle by applied force, contraction of trunk muscles, and gravity, causing a change in height of 1 to 1.5 mm or approximately a 15% change in volume.11,12 This slow cycling flushes out the free water loosely bound in the nucleus gel plus the nutrients and by-products.4,9,14,21,22 Firmly bound water within the hygroscopic gel does not fluctuate. Exchange of water and small molecular species occurs, but nutrients and waste products do not pass through the intact annulus; instead, the flow of these elements is through the end plates, across the thin, intact cartilage, and also through tiny (0.5 mm) perforations of the end plates.8,14,20,23 The flow is regulated by both applied and osmotic pressure gradients across the end plate. Through the tubular channels of these perforations, only small molecules are allowed to pass into the nucleus and inner annulus, while the potentially toxic anaerobic by-products pass out from them.8,20 At the outer end of these channels are located clumps of arteriolar tissue, which have been shown to behave like primitive glomeruli8,20 ( Fig. 4.2 (a,b) Diagram of the innervation and parallel vascularity of the outer annulus—both pass together in the belt around the annulus. ALL, anterior longitudinal ligament; PLL, posterior longitudinal ligament. The gray ramus and the accompanying somatosensory nerve pass together from the sensory ganglion to the autonomic ganglion. The small free nerve endings and arterioles penetrate the outer layers of the annulus at right angles and then arborize within the six outer annular layers. Fig. 4.3 Cross-section micrograph of the end plate of a rabbit disc showing the large venous passages of the vertebral spongiosa and a thin arteriolar layer just outside the end plate. The small clump of arteriolar tissue from which the descending passage originates is the equivalent microglomerulus. The descending tubular passage crosses the bony and cartilaginous end plate, through which nutrients and waste pass bidirectionally. (Reproduced with permission from Oki et al.8) With age there is a progressive loss of water within the nucleus pulposus leading to disc degeneration and disc space collapse. This process has been characterized using Thompson’s grading ( The process of disc degeneration can be reproduced in an animal model of disc degeneration by needle puncture of the annulus in rabbits, thus mimicking what occurs in humans with annular tears26 ( The accumulated anaerobic by-products of the nucleus and inner annulus are potentially neurotoxic. Lactic acid particularly accumulates in this anaerobic environment.4,15,16 When the internal pH is below 6.2, regeneration of the gel and inner annular fibers ceases. This is a major contributor to the degenerative cascade. Other by-products, such as metalloproteinases, stromelysin, and phospholipase A2, accumulate and are also neurotoxins.18,19 Thus, when the disc, like a belted automobile tire, loses its internal swelling pressure and its sidewalls or circumferential annular belts bulge, tears may occur.21,24,25 This result is much like a tire losing internal air pressure and flattening. In the disc, if the radial tears pass full thickness through the annulus, the neurotoxins may escape, and may reach and irritate the free nerve endings in the outer annular belt resulting in back and often radicular leg pain (see Fig. 4.4 Progressive loss of nucleus pulposus integrity seen with aging of the disc and classified using the Thompson grading system. Illustration from top to bottom shows grade 1 to 5 as the disc progressively degenerates. Both plant and animal cell walls have phospholipids that help regulate water loss. When cells die, fracture, or wear out, the remaining cell wall lipid debris must be solubilized so it can be removed by the circulation. In response to cell wall disruptions, a rate-limiting enzyme, phospholipase A2, is released to convert the insoluble cell wall lipids into soluble arachidonic acid, but in so doing also releases prostaglandins and leukotrienes, both drivers of inflammation and pain.19 The level of phospholipase A2 is related to the degree of tissue injury. Because the disc nucleus is essentially sealed, the accumulation of phospholipase A2 is higher than in any other tissue. In an experiment at the University of California, San Diego,19 discograms using injections of saline solution were performed on normal and degenerated discs of patients. Samples from the disc spaces in the same patients were injected into bilateral sciatic nerves of rats. The sciatic nerves injected with samples collected from individuals with normal disc morphology produced only a mild inflammation, whereas the fluid from patients with degenerative discs destroyed the sciatic nerve, partly paralyzing the animal.19 Therefore, the toxic material in degenerated discs, even in submicroscopic quantities, can be pumped out through annular tears by the motion of the disc and cause severe disabling back pain. Furthermore, if the nearby ganglion is also reached, there may be permanent damage with altered sensation and weakness of a limb. This is highlighted with the reproduction of concordant disabling back or leg pain after the injection of less than 0.5 mL of normal saline or X-ray-visible contrast dye in some patients with tiny annular radial tears.27
4.1 Introduction
4.1.1 Disc Physiology
Fig. 4.1). Inside the annular ring is contained an aggrecan, glycosaminoglycan, a protein-sugar complex gel having great hygroscopic (i.e., water holding) ability.9 The swelling pressure of this gel of the nucleus maintains the pressure within the annulus, forcing the vertebrae apart and tightening the annular fibers. This tightening provides the primary mechanical stability and flexibility of each discal segment of the spinal column.3,10,11 Further, the angulated arrangement of the fibers also controls the segmental stability and flexibility of the motion segment in multiple planes as motion can occur with six degrees of freedom. The same gel is also found in thin layers separating the annular laminar construction, providing some apparent elasticity and separating the laminations, reducing interlaminar torsional abrasion. With aging or degeneration, nucleus gel declines, while collagen content, including fibrosis, relatively increases.1,5,12,13,14
Fig. 4.2). C-fiber pain is sharp and highly localized, and serves as an early warning system, triggering protective reflexes such as local muscle contractions. The normal intact disc functions painlessly, even though the nucleus accumulates anaerobic metabolites that could stimulate the free nerve endings in the outer annulus and sensitive structures just outside the annulus.6,18,19,20 A potential source of chronic low back pain could be disruption of the annulus fibrosus and irritation of these nerve endings by extruded irritants originating in the nucleus pulposus. Additionally, the relatively close proximity of the dorsal root ganglion, a major origin of pain sensation, to the disrupted annulus fibrosus may also contribute to low back pain symptoms.
Fig. 4.3). Therefore, the passage of substances to and from the nucleus is controlled, allowing molecules smaller than about 200,000 Da (molecular diameters) to pass.4,14,20 Because body enzymes could destroy the hygroscopic behavior of the gel, this membrane acts as a protective barrier to enzyme passage. Changes in the end plate that alter the permeability of these microglomeruli will cause changes in the structure and behavior of the contained gel, then secondarily its mechanical behavior, and thirdly that of the annular fiber tightness, altering the stability of the entire segment. Potentially protecting and replenishing the gel could potentially preserve spinal stability and prevent discogenic back pain.4,5,11,12,24,25
Fig. 4.4).
Fig. 4.5).
Fig. 4.4).
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