Spinal Degeneration

In spinal degeneration, also termed spondylosis, disc degeneration seems to occur first. Changes to the biologic structure of the disc lead to the mechanical failure of that disc. Normally, annulus cells synthesize mostly collagen type I in response to deformation, whereas nucleus cells respond to hydrostatic pressure by synthesizing proteoglycans and fine collagen type II fibrils. Cell density declines during growth and is extremely low in the adult, especially in the nucleus. In adult discs, blood vessels are normally restricted to the outermost layers of the annulus. Metabolite transport is both by diffusion, which is important for small molecules, and by bulk fluid flow, which is important for large molecules. Low oxygen tension in the center of a disc leads to anaerobic metabolism, resulting in a high concentration of lactic acid and low pH. Chronic lack of oxygen causes nucleus cells to become quiescent, whereas a chronic lack of glucose can kill them. Deficiencies in metabolite transport appear to limit both the density and the metabolic activity of disc cells. As a result, discs have only a limited ability to recover from any metabolic or mechanical injury. Disc cells synthesize their matrix and break down an existing matrix by producing and activating degradative enzymes, including matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase (ADAM). The proteoglycan content of the disc is primarily responsible for the disc’s ability to act as a compressive buffer. It is maximal in the young adult and declines later on in life, presumably because of proteolysis. Disc cells appear to adapt the properties of their matrix to suit their environment. With increasing age, the overall proteoglycan and water content of the disc decreases, especially in the nucleus. There is a corresponding increase in collagen content, a tendency for fine type II collagen fibrils in the inner annulus to be replaced by type I fibers as the annulus encroaches on the nucleus, and a tendency for type I fibers throughout the disc to become coarser. Loss of proteoglycan fragments from the disc is a slow process owing to the entrapment of the nucleus by the fibrous annulus and the cartilage end plates of the vertebrae. Reduced matrix turnover in older discs enables collagen molecules and fibrils to become increasingly cross-linked with each other, and existing cross-links become more stable. In addition, reactions between collagen and glucose lead to “nonenzymatic glycation” causing even more cross-linking and imparting a yellow color to the aging disc. With increasing age, the hydrostatic nucleus becomes smaller and the proteoglycan content of the nucleus decreases. As such, its ability to hold water and withstand compressive loads declines. The annulus becomes stiffer and ultimately weaker.

Ultimately, aged discs fail to function properly and place additional strains on the facet joints and adjacent spinal motion segments. In the disc itself, the accumulated products of degeneration affect the metabolism of the remaining viable cells. This further hastens disc failure, resulting in changes that may be seen on magnetic resonance imaging (MRI). These MRI changes include decreased water content, which is visible on T2-weighted images and is termed dark disc disease ( Fig. 22-1 ). The result of this cascade of failure is disc collapse.

Sagital MRI showing dark disc disease.

(From Lavelle WF, Carl AL, Lavelle ED, Furdyna A: Back pain. In Smith H, editor: Current therapy in pain, 2009, Philadelphia: Saunders, pp 167–181.)

Isolated back pain may be due to a variety of forms of disc dysfunction. Pain may occur at any point of degeneration. Crock studied pain related to disc failure and coined the term internal disc derangement (IDD) in 1970. The term was used to describe a large group of patients whose disabling back and leg pain worsened after an operation for suspected disc prolapse. Internal disc derangement was intended to describe a condition marked by alterations in the internal structure and metabolic functions of the disc thought to be attributable to an injury or a series of injuries that may even have been subclinical. Despite Crock’s attempts to categorize disc failure, no direct and reliable relationship between measurable disc failure and pain has been developed.

Although the pathophysiology of IDD is complex, aging is correlated with changes in the intervertebral disc. NF-κB is a family of transcription factors that plays a major role in mediating the body’s response to damage. Chronic activation of NF-κB has been linked to tissue aging and many age-related degenerative diseases. Nasto and colleagues demonstrated that the NF-κB signaling pathway is a key mediator of age-dependent disc derangement. They used a mouse model to show that pharmacologic inhibition of NF-κB increased disc proteoglycan synthesis and lessened the loss of disc cellularity and matrix proteoglycans. They confirmed this finding by genetically depleting mice of a NF-κB subunit and repeating the study.

As the disc fails, additional degenerative changes to the surrounding spinal structures may also occur. Disc failure is often the first of a series of failures in the spine. It has been hypothesized that disc failure causes the spinal ligaments to buckle and hypertrophy because of exposure to excessive forces, including new torsion forces. These abnormal forces may cause instability. Facet joint degenerative changes are believed to follow. When pain arises from the facet joints, patients often complain of greater discomfort with spine extension or hyperextension. Once muscles weaken, as is often seen with any form of spinal degeneration, any position can cause discomfort. As the degeneration progresses, further instability and joint hypertrophy may result. Facet joint hypertrophy is the body’s attempt to stabilize the motion segments. Similar to the degenerative changes seen in large appendicular joints such as the knee, significant radiographic degeneration may be seen in patients that have little or no back pain. These degenerative changes may, however, cause impingement or stretch the neural elements, causing neuropathic pain.

In the most common scenario, more than one type of degenerative change is responsible for nerve compression. As the nerve roots traverse the spinal canal, they pass through regions adjacent to the facet joints termed the lateral recesses. In this region, they may be encroached on by any combination of hypertrophic facet joints, infolded ligamentum flavum, and perhaps bulging disc material. All of these changes result in nerve compression within the spinal canal.

Degenerative changes can also cause nerve root impingement in the neural foramen. The anteroposterior diameter of the foramen may be reduced by bulging disc material anteriorly and the hypertrophic facets posteriorly. Foraminal height is reduced merely by the loss of intervertebral disc height. Facet subluxation can further decrease foraminal volume, making the exiting nerve roots in these patients even more susceptible to the compression caused by small amounts of disc bulging or facet hypertrophy.

The areas of the degenerating spine may fail at different rates, leading to different clinical pictures of back pain, leg pain, or instability. If the anterior disc and ligaments fail at the same rate as the posterior structures, such as the facet joints, anterior subluxation of one vertebra is a possible result. This is termed spondylolisthesis. If this failure occurs asymmetrically and there is a rotational or lateral translation, the deformity is termed olisthesis. Degenerative spondylolisthesis is most common at the L4-5 level and occurs 6 to 10 times more often here than at any other level. It is more common in women than men and in African Americans than whites. The increased motion caused by disc degeneration, combined with decreased shear resistance, allows for the anterior slip. Degenerative spondylolisthesis at the L4-5 level may result in a combination of central stenosis with lateral recess stenosis that compresses the traversing L5 nerve roots. Degenerative spondylolisthesis rarely exceeds 35% translation of the vertebrae.

The posterior elements of the vertebra may also be disrupted by a stress fracture of an area of the spine called the pars interarticularis. The pars interarticularis is the lateral part of the posterior element that connects the superior and inferior facets. (The term literally means “part between the articulations.” By definition, pars interarticularis means “part between the articulations.”) Repetitive flexion-extension and rotation lead to microtrauma at this junction and thereby fracture. Studies show that most patients with a spondylolysis or isthmic spondylolisthesis are unlikely to be at risk for increased back pain symptoms.

Neuropathic Pain in Spinal Degeneration

There are primarily two types of pain that result from degenerative spinal disease: radicular pain and claudication pain. Radicular pain, or radiculitis, is pain that radiates along a dermatome of a nerve. This may be due to inflammation, pressure, or stretch of the nerve root. Claudication pain is more difficult for patients to describe. When forced to describe this type of pain, patients may describe it as leg cramping, “aching,” or heaviness that reliably occurs with walking. Claudication is often associated with spinal stenosis. Spinal stenosis is the narrowing of the spinal canal due to any of the causes described previously, including hypertrophy of the ligaments, facets, or discs. This topic will be reviewed in detail in a later chapter.

The exact pathophysiology of the mechanisms of radicular and claudication pain remains elusive. The sequences of neuropathologic changes that result from neurologic compression in the lumbar spinal canal have been investigated in animal studies. Delamarter and colleagues used a dog model in which they created varying degrees of stenosis and demonstrated deleterious effects on the neural elements by increasing the degree of the stenosis. They found that cortical evoked potentials were highly sensitive to this compression and were affected long before any clinical signs occurred. These authors also demonstrated venous congestion and arterial constriction around compressed nerve roots and dorsal root ganglia. The result was blockage of axoplasmic flow, with resulting edema, demyelination, and Wallerian degeneration of motor and sensory fibers. Other authors have shown that sensory fibers are more susceptible to pressure and slower to recover than motor fibers, which may explain the presence of subjective sensory changes in the absence of objective physical findings. Arnoldi and coworkers suggested that increased venous pressure may explain the symptoms of neurogenic claudication. Others have suggested that narrowing of the spinal canal may lead to a reduction in blood supply to the cauda equina, resulting in ischemic changes from the diffusion of metabolites. These changes may stimulate the sinuvertebral nerve or lead to secretion of pain mediators, such as substance P, from the dorsal root ganglion. Perineural inflammation of unknown origin may also result in pain generation.

The majority of literature examining the causes of neurologic pain resulting from spinal pathology attributes compression as the principal cause. However, there are instances where patients have persistent neuropathic pain, particularly radicular symptoms in the absence of imaging studies displaying compressive pathology.