Modified from Woolf CJ; American College of Physicians; American Physiological Society. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med 2004;140:441-451.

Adaptive Pain

“The good”

Pain that contributes to survival by protecting the organism from injury or promoting healing when injury has occurred (nociceptive pain)

Coupled from a noxious stimulus or healing tissue

Maladaptive Pain

“The bad and the ugly”

An expression of the pathologic operation of the nervous system (neuropathic pain) or abnormal operation of the nervous system (functional pain)

Uncoupled from a noxious stimulus or healing tissue

Pain as disease

Multiple mechanisms that can produce pain, as follows:

Nociception: The sole mechanism that causes nociceptive pain and is comprised of the processes of transduction, conduction, transmission, and perception.

Transduction: The conversion of a noxious thermal, mechanical, or chemical stimulus into electrical activity in the peripheral terminals of nociceptor sensory fibers. This process is mediated by specific receptor ion channels expressed only by nociceptors (Fig. 2-3).

Conduction: The passage of action potentials from the peripheral terminal along axons to the central terminal of nociceptors in the central nervous system.

Transmission: the synaptic transfer and modulation of input from one neuron to another (Fig. 2-4).

Central sensitization: Contributes to inflammatory, neuropathic, and functional pain (Figs. 2-3 and 2-5).

Figure 2–3 A, The peripheral terminal of a nociceptor sensory neuron. The different transducing receptor and ion channels that respond to thermal, mechanical, and chemical stimuli are shown. MDEG, mammalian degenerin; P2X, purinergic receptor; TRM3, 2’-O-ribose methyltransferase 3. B, The mechanism of peripheral sensitization. Inflammatory mediators, such as prostaglandin E₂ (PGE₂), bradykinin (BK), and nerve growth factor (NGF), activate intracellular kinases in the peripheral terminal that phosphorylate transducer channels to reduce their threshold or sodium channels to increase excitability. C, Transcriptional changes in the dorsal root ganglion (DRG). Activity, growth factors, and inflammatory mediators act on sensory neurons to activate intracellular transduction cascades. These cascades control the transcription factors that modulate gene expression, leading to changes in the levels of receptors, ion channels, and other functional proteins. AA, arachidonic acid; ASIC, acid-sensing ion channel; ATP, adenosine triphosphate; CaMKIV, calcium/calmodulin-dependent protein kinase IV; Cox2, cyclooxygenase-2; ERK, extracellular signal-regulated kinase; EP, prostaglandin E receptor; JNK, jun kinase; mRNA, messenger RNA; Na_v1.8/1.9, voltage gated sodium channel type 1.8/1.9; NGF, nerve growth factor; P38, serinethreonine kinase; PKA, protein kinase A; PKC, protein kinase C; TRP, transient receptor potential.

(From Woolf CJ: Pain: Moving from symptom control toward mechanism-specific pharmacologic management.Ann Intern Med 2004;140:441-451.)

Figure 2–4 Contributions of spinal cord dorsal horn neurons to pain. A. Nociceptive transmission. B. The acute phase of central sensitization. C. The late phase of central sensitization. Some alterations in gene expression are activity-driven and restricted, such as dynorphin, whereas others are widespread and produce diverse changes in function, such as induction of cyclooxygenase-2 (COX-2) in central neurons after peripheral inflammation. D. Disinhibition. AA, arachidonic acid; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate; EP, prostaglandin E receptor; IL-1, interleukin-1; NK1, neurokinin 1; NMDA, N-methyl-D-aspartic acid; PGE2, prostaglandin E2.

(From Woolf CJ: Pain: Moving from symptom control toward mechanism-specific pharmacologic management.Ann Intern Med 2004;140:441-451.)

Figure 2–5 Scheme of the Major Signaling Pathways that Regulate TRP Ion Channels. (+) represents sensitization or activation; (−) represents desensitization. In the early phase of inflammation, increased pain sensitivity originates largely as a result of the local release from inflammatory cells of a number of mediators. Most of these inflammatory mediators do not directly activate nociceptors, but rather act as sensitizers, reducing the threshold of the peripheral nociceptor terminals. Among the major inflammatory mediators are prostanoids, particularly prostaglandin E₂ (PGE₂), bradykinin, and nerve growth factor. These chemicals acting through EP prostaglandin and B₁/B₂ bradykinin G protein-coupled receptors and the high-affinity TrkA NGF receptor produce their immediate effects on pain hypersensitivity locally on the nociceptor terminals by phosphorylating TRPV1 as well as the sensory neuron-specific voltage-gated sodium channel Nav 1.8. Activation of the protease-activated receptor 2 by inflammatory proteases like trypsin has a similar effect. Phosphorylation and dephosphorylation substantially alter TRPV1 ion channel function, and this represents a major means of rapidly and dynamically altering pain sensitivity. AA, arachidonic acid; AC, adenylate cyclase; AKAP, A-kinase anchor proteins; B₂R, bradykinin receptor 2 (BDKRB2); CaM, calmodulin; CaMKII, calmodulin dependent kinase II; COX, cyclooxygenase; DAG, diacylglycerol; EET, epoxyeicosatrienoic acids; EP, prostaglandin E; ER, endoplasmic reticulum; ERK, extracellular-signal-regulated kinases; G11, guanine nucleotide-binding (G) protein-subunits 11; HPETE, hydroperoxyeicosatetraenoic acid; IP₃R, inositol 1,4,5-trisphosphate receptor; LOX, lipooxygenase; NGF, nerve growth factor; PIP₂, phosphatidylinositol 4,5-bisphosphate; PIP₃, phosphatidylinositol (3,4,5)-trisphosphate; PI3K, phosphatidylinositol 3-kinases; PKA, protein kinase A; PKC, protein kinase C; PLA2, phospholipases A2; PLC, phospholipase C; PP2B, protein phosphatase 2B (Calcineurin (CN)); P38, mitogen-activated protein kinases; P450, cytochrome P450; Src, a family of proto-oncogenic tyrosine kinases, Rous sarcoma virus (RSV); Trk A, tyrosine kinase A; TRP, transient receptor potential (has TRPV, TRPM, TRPA, and TRPC subfamilies).

(Modified from Wang H, Woolf CJ. Pain TRPs. Neuron 2005;46:9-12.)

Figure 2–6 Effect of the presence (panel A) and absence (panel B) of downstream regulatory element antagonistic modulator (DREAM) on nociceptive processing after noxious stimulation of the skin with a pin. In panel A, the prodynorphin gene is blocked by DREAM, and the nociceptive signal is transmitted by substance P (SP)-containing dorsal root neurons essentially unaltered through the spinal cord. This activated state is characterized by a large depolarizing potential and multiple spike discharges. Such activity subsequently activates systems governing descending regulatory control and thalamic nuceli, triggering the perception of pain. In panel B, DREAM has been knocked out, and the release of dynorphin from spinal cord interneurons becomes a prominent part of the nociceptive response. This inactivates spinal-projection neurons, leading to a greatly reduced excitatory response. Subsequently, there is almost complete inactivation of descending regulatory and pain-processing systems. In addition to raising issues related to the specific functions of DREAM, this simple scheme emphasizes the importance of neurophysiological research involving this model and hypotheses to guide drug design.

(From Vogt BA. Knocking out the DREAM to study pain.N Engl J Med 2002; 347: 362-364.)

Ectopic excitability, structural reorganization, and decreased inhibition are unique to neuropathic pain, whereas peripheral sensitization occurs in inflammatory pain and in some forms of neuropathic pain.

Pain transient receptor potential (TRP) ion channels are listed in Table 2.2 and illustrated in Figure 2-6. TRP ion channels are molecular gateways in sensory systems, an interface between the environment and the nervous system. Several TRPs transduce thermal, chemical, and mechanical stimuli into inward currents, an essential first step in eliciting thermal and pain sensations.

Table 2.2 Mammalian Sensory Transient Receptor Potentials (TRPs)

Facet joint pain

Definition

The facet, or zygapophyseal, joint is the set of paired diarthrodial articulations between the posterior elements of the adjacent vertebrae.

Facet joints have been implicated as responsible for spinal pain in 39% of patients with neck pain, 34% of patients with thoracic pain, and 27% of patients with low back pain [1].

Innervations

The nerve roots are invested by pia mater and covered by arachnoid and dura as far as the spinal nerve. The dura of the dural sac continues around the roots as their dural sleeve, which blends with the epineurium of the spinal nerve (Fig. 2-7).

Figure 2–7 Spinal nerves.

(From Schuenke M, Schulte E, Schumacher U, et al [eds]: Thieme Atlas of Anatomy: General Anatomy and Musculoskeletal System. Stuttgart, Thieme, 2006, p 62.)

Facet joints are well innervated by the medial branches of the dorsal rami, which contain free and encapsulated nerve endings as well as nociceptors and mechanoreceptors. Each segmental medial branch of the dorsal ramus supplies at least two (in humans, monkeys, and cats) or three (in rats) facet joints (Table 2.3).

▪ In the cervical spine below C2-C3, the cervical facet joints are supplied by the medial branches of the cervical rami above and below the joint, which also innervate the deep paramedian muscles.

▪ The C2-C3 joint is supplied by the third occipital nerve.

▪ Innervation of the atlantooccipital and atlantoaxial joints is derived from the C1 and C2 roots, respectively.

▪ In the thoracic and lumbar spine, the facet joints are innervated by medial branches of the dorsal rami of the spinal nerves except at the L5 level.

▪ The L5 dorsal ramus divides into medial and lateral branches, with the medial branch continuing medially, innervating the lumbosacral joint.

Table 2.3 The Lumbar Spinal Nerves

Situations that can lead to pain upon facet joint motion are degeneration, inflammation, and injury of the facet joint.

Pain leads to restriction of motion, which eventually leads to overall physical deconditioning. Irritation of the facet joint innervation in itself also leads to secondary muscle spasm.

The facet has extensive innervation of the synovial lining by small C-type pain fibers, as evidenced by the following findings:

▪ An abundance of protein gene product 9.5 (PGP 9.5)–reactive nerve fibers indicates an extensive innervation of the facet joint capsules.

▪ There are nerve fibers to the facet joint capsules that are reactive to both substance P (SP) and calcitonin gene–related peptide (CGRP) [2].

Intervertebral disc

The three components of the intervertebral disc (IVD) are as follows:

End plate: This structure consists of a layer of cartilage, resembling articular cartilage that covers the central parts of the inferior and superior cortical bone surfaces of the vertebral bodies.

Nucleus pulposus: The space between the end plates of adjacent vertebrae is filled by the nucleus pulposus (NP), which consists of chondrocytes within a matrix of type II collagen and proteoglycans, mainly aggrecan. The type II collagen fibers are not believed to give the same level of order to the structure or the same degree of mechanical stability to the matrix as in articular cartilage. The proteoglycans are hydrophilic, causing the NP to swell. The swelling pressure of the NP proteoglycans is constrained by the end plates above and below and the anulus fibrosus around the periphery. On tissue sections stained with hematoxylin and eosin, the NP appears homogeneous and pale lilac-blue, consistent with its complement of proteoglycans. In polarized light, it exhibits little birefringence.

Anulus fibrosus: This structure comprises dense sheets of highly ordered collagen fibers (mainly type I but also types II and III) in which are cells with the morphology and phenotype of fibroblasts. Functionally, the anulus fibrosus (AF) is a very strong ligament binding together the outer rims of adjacent vertebrae. On tissue sections stained with hematoxylin and eosin, the AF exhibits fairly uniform eosinophilia, and in polarized light, its constituent alternating bands of highly orientated collagen fibers are clearly seen.

Distinguishing “Normal Aging” from Disease of the Intervertebral Disc

Figures 2-8 and 2-9 and Table 2.4 contain information pertinent to this issue.

Figure 2–8 Questionable radiographic diagnoses that increase in frequency with age, from imaging studies of patients without symptoms. CT, computed tomography; DJD, degenerative joint disease; MRI, magnetic resonance imaging.

(From Loeser JD: Low back pain. In Loeser JD, Butler SH, Chapman CR, Turk DC [eds]: Bonica’s Management of Pain, 3rd ed. Philadelphia, Lippincott Williams & Wilkins, 2001, p 1520.)

Figure 2–9 Forces within the nucleus pulposus and annulus of a nondegenerated disc (left) and degenerated disc (right) under compression.

(From Urban JPG, Roberts S: The intervertebral disc: Normal, aging, and pathologic. In Herkowitz HN, Garfin SR, Eismont FJ, et al [eds]: Rothman-Simeone The Spine, 5th ed. Philadelphia, Saunders, 2006, p 133.)

Table 2.4 Pathophysiology of Intervertebral Disc Aging and Degeneration

Process	Effects
Diminished cellular response	Senescence (alteration in gene expression and transcription factors)
	Apoptosis (programmed cell death)
Biochemical processes	Imbalance between catabolic and anabolic activity: Post-translational protein modification Increased collagen cross-linking through nonenzymatic glycation, lipid peroxidation Loss of proteoglycans Altered diffusion of nutrients Impaired assembly of newly synthesized molecules

End plate changes Diminished vascularity and decreased porosity because of end plate calcification → elevated lactate concentrations and reduced pH → cell apoptosis Thinning or microfracture of the end plate → increased permeability and altered hydraulic property → nonuniform load transference and increased focal shear stress → disc degeneration and anular damage

From Biyani A, Andersson GBJ: Low back pain: Pathophysiology and management.J Am Acad Orthop Surg 2004;12:106-115.

(Reprinted from Urban JPG, Roberts S: The intervertebral disc: Normal, aging, and pathologic. In Herkowitz HN, Garfin SR, Eismont FJ, et al [eds]: Rothman-Simeone The Spine, 5th ed. Philadelphia, Saunders, 2006, p 77.)

The implication of these findings is that although either angiogenesis or neuronogenesis could be targets for therapy, angiogenesis drives nerve ingrowth and may be more significant from a therapeutic perspective.

Cytokines as regulators of disease processes

There has also been growing interest in the possible role of cytokines in regulating the connective tissue degradation, nerve and vessel ingrowth, and macrophage accumulation that characterize IVD degeneration (Table 2.5) [4,5]. A number of cytokines have been implicated, including TNF (tumor necrosis factor) (Fig. 2-11), IL-1 (interleukin-1), IL-6, and IL-10, PDGF (platelet-derived growth factor), VEGF (vascular endothelial growth factor), IGF-1 (insulin-like growth factor-1), TGF-β (transforming growth factor-β), EGF (epidermal growth factor), and FGF (fibroblast growth factor) [6].

Table 2.5 Common Chemical Substances and Their Functions

Chemical Substance	Function
Phospholipase A₂	Mediates mechanical hyperalgesia
Nitric oxide	Inhibits mechanical hyperalgesia and produces thermal hyperalgesia
MMP-2 (gelatinase A) and MMP-9 (gelatinase)	Degrade gelatin (denatured fibrillar collagens) and other matrix molecules Act synergistically with MMP-1

MMP-1 (collagenase-1) Degrades collagen MMP-3 (stromelysin-1) Both MMP-1 and MMP-2 may play a role in spontaneous regression of the herniated disc IL-1, TNF-α, prostaglandin E₂

Promote matrix degradation

Enhance production of MMPs

Calcitonin gene–related peptide, glutamate, substance P (neurotransmitters) Modulate dorsal root ganglion responses IL-6 Induces synthesis of TIMP-1 TIMP-1 Inhibits MMPs Transforming growth factor-β superfamily Blocks synthesis of MMPs Insulin-like growth factor-1, platelet-derived growth factor Have an anti-apoptotic effect

IL, interleukin; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase.

From Biyani A, Andersson GBJ: Low back pain: Pathophysiology and management.J Am Acad Orthop Surg 2004;12:106-115.

Figure 2–11 Suggested mechanism of action for tumor necrosis factors (TNF). A, TNF from cells of the herniated nucleus pulposus enters endothelial adhesion molecules such as intracellular and vascular cellular adhesion molecules (ICAM and VCAM). B, Circulating white blood cells adhere to the vessel walls (1) and extravasate from the capillaries out among the axons due to a TNF-induced increase in vascular permeability (2). TNF also induces an accumulation of thrombocytes that will form an intravascular thrombus (3). C, There is a local release of TNF from the extravasated white blood cells among the axons that will induce myelin injury, an accumulation of sodium channels, and allodynic events in the dorsal root ganglion (DRG) and at the spinal cord level. The thrombus, together the edema due to the increased permeability, will induce a nutritional deficit in the nerve root. Both the local effects of TNF and the nutritional deficit may induce pain and nerve dysfunction.

(From Olmarker K, Myers R, Kikuchi S, Meyers RR: Sciatica and nerve root pain in disc herniation and spinal stenosis: a basic science review and clinical perspective. In Herkowitz HN, Gardin SR, Eismont FJ, Bell GR, Balderston RA [eds]. Rothman-Simeone The Spine, 5th ed. Philadelphia, Saunders, 2006, p 101.)

Studies of IL-1 have yielded the following findings:

▪ IL-1 has a role in maintaining cartilage homeostasis, largely through its ability to switch chondrocytes from anabolism to catabolism, inducing cartilage breakdown at molecular and morphologic levels.

▪ It is a regulator of angiogenesis in joints and nonarticular cartilage, possibly by acting as a promoter of the potent angiogenic factor VEGF.

▪ In the IVD, both of the isoforms, IL-1α and IL-1β, have been shown to increase proteoglycan release and degradative enzyme production.

▪ IL-1α and IL-1β have also been found to increase the production of MMPs and pain mediators, such as the eicosanoid prostaglandin E₂, by human IVD cells.

▪ IL-1 can mediate some of the other characteristics of IVD disease, such as nerve and vessel ingrowth.

As IL-1 is the regulator of cartilage catabolism, the TGF-β superfamily is the regulator of cartilage anabolism. A twofold increase was seen in proteoglycan synthesis by rabbit nucleus pulposus cells after injection of rabbit intervertebral discs with an adenoviral vector carrying a human TGF-β transgene [6].

Nomenclature and classification of lumbar disc pathology

The North American Spine Society (NASS), the American Society of Spine Radiology (ASSR), and the American Society of Neuroradiology (ASNR) have determined nomenclature for and classification of lumbar disc pathology, which are summarized here.

General classifications of disc lesions are listed in Box 2.3 and described here:

Normal disc: A disc is considered normal if it is young and morphologically normal, without consideration of the clinical context. This would not include degenerative, developmental, or adaptive changes that could, in some contexts (e.g., normal aging, scoliosis, and spondylolisthesis) be considered clinically normal. However, the bilocular appearance of the adult nucleus resulting from the development of a central horizontal band of fibrous tissue is considered a sign of normal maturation. The disc space is defined craniad and caudad by the vertebral body end plates and peripherally by the outer edges of the vertebral ring apophyses, exclusive of osteophytic formations.

Congenital/developmental variant: This category includes discs that are congenitally abnormal or that have undergone changes in their morphology as an adaptation to abnormal growth of the spine, such as from scoliosis or spondylolisthesis.

Degenerative/traumatic: The use of the terms degenerative and traumatic to describe this group does not imply that trauma is necessarily a factor or that degenerative changes are necessarily pathologic. These changes may be a result of the normal aging process.

Anular tears: Also properly called “anular fissures,” anular tears are separations between anular fibers, avulsion of fibers from their vertebral body insertions, or breaks through fibers that extend radially, transversely, or concentrically, involving one or many layers of the anular lamellae. “Tear” and “fissure” describe the spectrum of such lesions and do not imply that the lesion is consequent to trauma (Fig. 2-12).

Degeneration: Disc degeneration may involve any or all real or apparent desiccation, fibrosis, narrowing of the disc space, diffuse bulging of the anulus beyond the disc space, extensive fissuring (i.e., numerous anular tears), and mucinous degeneration of the anulus, defects and sclerosis of the end plates, and osteophytes at the vertebral apophyses. A disc demonstrating one or more of these degenerative changes can be further qualified into one of two subcategories, spondylosis deformans—possibly representing changes in the disc associated with a normal aging process—and intervertebral osteochondrosis—possibly the consequence of a more clearly pathologic process (Fig. 2-13).

Herniation: Herniation is defined as a localized displacement of disc material beyond the limits of the intervertebral disc space (Fig. 2-14). Disc material may be nucleus, cartilage, fragmented apophyseal bone, anular tissue, or any combination thereof.

BOX 2.3 General Classification of Disc Lesions*

Modified from Milette PC: Classification, diagnostic imaging, and imaging characterization of a lumbar herniated disc. Radiol Clin North AM 2000;38:1267-1292.

1. Normal (excluding aging changes)

2. Congenital/developmental variant

4. Inflammation/infection

5. Neoplasia

6. Morphologic variant of unknown significance

Figure 2–12 Schematic sagittal anatomic sections showing the differentiating features of a normal disc, an anular tear (radial tear in this case), and a disc herniation. The term tear is used to refer to a localized radial, concentric, or horizontal disruption of the anulus without associated displacement of disc material beyond the limits of the intervertebral disc space. Nuclear material is shown in red, and the anulus (internal and external) corresponds to the gray portion of the intervertebral space.

(From Milette PC: Classification, diagnostic imaging and imaging characterization of a lumbar herniated disc. Radiol Clin North Am 2000;38:1267-1292.)

Figure 2–13 Schematic sagittal anatomic sections showing the differentiating characteristics of a normal disc, spondylosis deformans, and intervertebral osteochondrosis. The distinction between these three entities is usually possible on all imaging modalities, including conventional radiographs.

(From Milette PC: Classification, diagnostic imaging and imaging characterization of a lumbar herniated disc. Radiol Clin North Am 2000;38:1267-1292.)

Figure 2–14 Herniated disc refers to localized displacement of nucleus, cartilage, fragmented apophyseal bone, or fragmented anular tissue beyond the intervertebral disc space (disc space, interspace). The interspace is defined, craniad and caudad, by the vertebral body end plates. Two intravertebral herniations, one with an upward orientation and the other with a downward orientation with respect to the disc space, are illustrated schematically.

(Adapted from Fardon DF, Milette PC; Combined Task Forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology: Nomenclature and classification of lumbar disc pathology: Recommendations of the Combined Task Forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology. Spine 2001;26:E93-E113.)

Classifications of Disc Herniation

Figure 2-15 illustrates, and Box 2.4 summarizes, the proposed categories for the description and classification of disc herniation, which are as follows [7]:

▪ Generalized disc herniation: defined as greater than 50% (180 degrees) of the periphery of the disc.

▪ Localized displacement in the axial (horizontal) plane, which is further classified as focal (involving less than 25% of the disc circumference) or broad-based (involving between 25% and 50% of the disc circumference.

Figure 2–15 The interspace is defined, peripherally, by the edges of the vertebral ring apophyses, exclusive of osteophytic formations. A, The line drawing schematically illustrates a localized extension of disc material beyond the intervertebral disc space, in a left posterior direction, which qualifies as a disc herniation. B, For classification purposes, the intervertebral disc is considered a two-dimensional round or oval structure having four 90-degree quadrants. By convention, a herniation is a localized process involving less than 50% (180 degrees) of the disc circumference. C, By convention, a focal herniation involves less than 25% (90 degrees) of the disc circumference. D, By convention, a broad-based herniation involves between 25% and 50% (90 to 180 degrees) of the disc circumference. E, Symmetrical presence (or apparent presence) of disc tissue circumferentially (50%-100%) beyond the edges of the ring apophyses may be described as a “bulging disc” or “bulging appearance” and is not considered a form of herniation. Furthermore, bulging is a descriptive term for the shape of the disc contour and not a diagnostic category. F, Asymmetrical bulging of the disc margin (50%-100%), such as found in severe scoliosis, is also not considered a form of herniation. Herniated discs may take the form of protrusion (G) or extrusion (H), according to the shape of the displaced material.

BOX 2.4 Proposed Categories for Description and Classification of a Disc Herniation

Modified from Fardon DF, Milette PC; Combined Task Forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology: Nomenclature and classification of lumbar disc pathology: Recommendations of the Combined Task Forces of the North American Spine Society, American Society of Spine Radiology, and American Society of Neuroradiology. Spine 2003;26:E93-E113.

4. Relation with posterior longitudinal ligament complex

5. Volume

6. Composition

7. Location

Bulging disc, which is defined as the presence of disc tissue “circumferentially” (50%-100%) beyond the edges of the ring, is not considered a form of herniation, nor are diffuse adaptive alterations of disc contour secondary to an adjacent deformity as may be present in severe scoliosis or spondylolisthesis.

The distinction between protrusion and extrusion of a disc herniation is clarified by Figures 2-16 and 2-17.

Figure 2–16 When a relatively large amount of disc material is displaced, distinction between protrusion (A) and extrusion (B or C) generally possible only on sagittal magnetic resonance images or sagittal computed tomography (CT) reconstructions. C, Although the shape of the displaced material is similar to that of a protrusion, the greatest craniocaudal diameter of the fragment is greater than the craniocaudal diameter of its base at the level of the parent disc, and the lesion therefore qualifies as an extrusion. In any situation, the distance between the edges of the base, which serves as reference for the definition of protrusion and extrusion, may differ from the distance between the edges of the aperture of the anulus, which cannot be assessed on CT scans and is seldom appreciated on MR images. In the craniocaudal direction, the length of the base cannot exceed, by definition, the height of the intervertebral space.

(From Milette PC: Classification, diagnostic imaging and imaging characterization of a lumbar herniated disc. Radiol Clin North Am 2000;38:1267-1292.)

Figure 2–17 Schematic representation of various types of posterior central herniations. A, Small subligamentous herniation (or protrusion) without significant disc material migration. B, Subligamentous herniation with downward migration of disc material under the posterior longitudinal ligament (PLL). C, Subligamentous herniation with downward migration of disc material and sequestered fragment.

(From Milette PC: Classification, diagnostic imaging and imaging characterization of a lumbar herniated disc. Radiol Clin North Am 2000;38:1267-1292.)

Complications of herniated discs are illustrated in Figure 2-18.

Figure 2–18 Relationship of typical posterior disc herniations with the posterior longitudinal ligament (PLL). A, Midline sagittal section. Unless very large, a posterior midline herniation usually remains entrapped underneath the deep layer of the PLL, and sometimes a few intact outer anulus fibers join with the PLL to form a “capsule.” The deep layer of the PLL (arrow) also attaches to the posterior aspect of the vertebral body so that no potential space is present underneath. B, Sagittal paracentral section. The PLL extends laterally at the disc level (arrow) but above and below the disc, an anterior epidural space (as), where disc fragments are frequently entrapped, is present between the lateral (peridural) membranes and the posterior aspect of the vertebral bodies.

(From Milette PC: Classification, diagnostic imaging and imaging characterization of a lumbar herniated disc. Radiol Clin North Am 2000;38:1267-1292.)

Figures 2-19 through 2-22 summarize the nomenclature for the anatomic zones and levels of the spine.

Figure 2–19 Coronal drawing illustrating the main anatomic zones and levels of a spinal segment.

Figure 2–20 Schematic representation of the anatomic zones of the vertebral body identified on axial images. The anterior zone (not shown) is delineated from the extraforaminal zone by an imaginary coronal line in the center of the vertebral body.

Figure 2–21 Schematic representation of the anatomic levels of a spinal segment identified on craniocaudal images.

Figure 2–22 Schematic summative representation of anatomic levels and zones of a spinal segment.

Dorsal root ganglion

Edema in the dorsal root ganglion is the basis of the production of nerve root pain in patients with disc herniation. Mechanosensitivity and chemosensitivity of the dorsal root ganglion have been demonstrated. Experimentally applied nucleus pulposus from both healthy and degenerative discs reduces nerve root conduction velocity, suggesting a pathomechanism of neural injury. The pertinent findings are as follows:

▪ The nucleus pulposus can induce excitatory changes, rising endoneurial pressures, and compartment syndrome, and can cause intraneural thrombi in the DRG or the nerve roots.

▪ Anti-inflammatory agents, such as tumor-necrosis factor-α (TNF-α) inhibitors, may protect against nucleus pulposus–induced injury to the DRG and nerve roots.

Sacroiliac joint

The pain sensitivity of the sacroiliac joints may be lower than that of lumbar facet joints but higher than that of the anterior portions of the lumbar discs. A high prevalence of sacroiliac joint pain may be seen in patients with post–lumbar fusion pain.

Postlaminectomy syndrome

Animal models of postlaminectomy syndrome demonstrate paraspinous muscle spasms, tail contractures, behavioral pain behaviors, tactile allodynia, epidural and perineural scarring, and adherence of the nerve root to the underlying disc and pedicle.

Facet joint involvement in chronic pain following lumbar surgery has been shown to be present in approximately 8% to 16% of patients. Through the use of a single nerve block, one study found the prevalence of sacroiliac joint pain following lumbar fusion to be 35% [8].

Epidural fibrosis may occur after an annular tear, disc herniation, hematoma, infection, surgical trauma, vascular abnormalities, or intrathecal injection of contrast media. Epidural fibrosis may account for as much as 20% to 36% of all cases of failed back surgery syndrome. Alternatively, there may be a final common pathway for all these etiologies that results in peripheral and central facilitation potentiated by inflammatory and nerve injury mechanisms. Paraspinal muscles may also become denervated and involved in the pathogenesis of failed back surgery syndrome [8].

Spinal stenosis

Spinal stenosis can be defined as a narrowing of the spinal canal that results in symptoms and signs due to entrapment and compression of the intraspinal vascular and nervous structures. Disc bulging, protrusion, and herniation in the cervical as well as lumbar areas, combined with osteophytes and arthritic changes of the facet joints, can cause narrowing of the spinal canal, encroachment on the contents of the dural sac, or localized nerve root canal stenosis (Fig. 2-23).

Figure 2–23 Algorithm describing pathogenesis of lumbar stenosis. DDD, Degenerative Disc Disease.

(Adapted from Akuthota V, Lento P, Sowa G: Pathogenesis of lumbar spinal stenosis pain: Why does an asymptomatic stenotic patient flare? Phys Med Rehabil Clin North Am 2003;14:17-28.)

References

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