Low Back Pain and Sciatica

Low Back Pain and Sciatica(eMedicine.com) Overview

Like a modern skyscraper, the human spine defies gravity, and defines us as vertical bipeds. It forms the infrastructure of a biological machine that anchors the kinetic chain and transfers biomechanical forces into coordinated functional activities. The spine acts as a conduit for precious neural structures and possesses the physiological capacity to act as a crane for lifting and a crankshaft for walking.

Subjected to aging, the spine adjusts to the wear and tear of gravity and biomechanical loading through compensatory structural and neurochemical changes, some of which can be maladaptive and cause pain, functional disability, and altered neurophysiologic circuitry. Some compensatory reactions are benign; however, some are destructive and interfere with the organisms capacity to function and cope. Spinal pain is multifaceted, involving structural, biomechanical, biochemical, medical, and psychosocial influences that result in dilemmas of such complexity that treatment is often difficult or ineffective.[1]Low back pain (LBP) is defined as chronic after 3 months because most normal connective tissues heal within 6-12 weeks, unless pathoanatomic instability persists. A slower rate of tissue repair in the relatively avascular intervertebral disk may impair the resolution of some persistent painful cases of chronic LBP (cLBP). An estimated 15-20% develop protracted pain, and approximately 2-8% have chronic pain. Of those individuals who remain disabled for more than 6 months, fewer than half return to work, and after 2 years of LBP disability, a return to work is even more unlikely.[2]Recent studies suggest that one third to one fourth of patients in a primary care setting may still have problems after 1 year.[3, 4]cLBP is the most common cause of disability in Americans younger than 45 years.[5, 6]Each year, 3-4% of the US population is temporarily disabled, and 1% of the working-age population is totally and permanently disabled.[7, 3, 8]LBP has been cited as the second most frequent reason to visit a physician for a chronic condition[3, 8, 9, 10], the fifth most common cause for hospitalization[3, 11, 12, 13], and the third most frequent reason for a surgical procedure.[3, 11, 12, 13]The socioeconomic impact of cLBP is massive. Ironically, a minority of patients with cLBP and disability due to cLBP account for the majority of the economic burden.[14, 15, 16]Most commonly, diagnoses of acute painful spinal conditions are nonspecific, such as neck or back strain, although injuries may affect any of several pain-sensitive structures, which include the disk, facet joints, spinal musculature, and ligamentous support.[17, 18]The origin of chronic back pain is often assumed to be degenerative conditions of the spine; however, controlled studies have indicated that any correlation between clinical symptoms and radiological signs of degeneration is minimal or nonexistent.[6, 17, 18, 19, 20, 21]Inflammatory arthropathy, metabolic bone conditions, and fibromyalgia are cited in others as the cause of chronic spine-related pain conditions.[17, 18]Although disk herniation has been popularized as a cause of spinal and radicular pain, asymptomatic disk herniations on computed tomography (CT) and magnetic resonance imaging (MRI) scans are common.[21, 22, 23, 24]Furthermore, there is no clear relationship between the extent of disk protrusion and the degree of clinical symptoms.[25]Degenerative change and injury to spinal structures produce lower back and leg pain that vary proportionally. A strictly mechanical or pathoanatomical explanation for LBP and sciatica has proved inadequate; therefore, the role of biochemical and inflammatory factors remains under investigation. In fact, this failure of the pathological model to predict back pain often leads to an ironic predicament for the patient with LBP.

Sciatica describes leg pain that is localized in the distribution of one or more lumbosacral nerve roots, typically L4-S2, with or without neurological deficit.[17, 18]However, physicians often refer to leg pain from any lumbosacral segment as sciatica. When the dermatomal distribution is unclear, the descriptive phrasenonspecific radicular pattern" has been advocated. When initially evaluating a patient with lower back and leg pain, the physician must first determine that pain symptoms are consistent with common activity-related disorders of the spine resulting from the wear and tear of excessive biomechanical and gravitational loading that some traditionally describe as mechanical.[18, 26]Mechanical lumbar syndromes are typically aggravated by static loading of the spine (eg, prolonged sitting or standing), by long lever activities (eg, vacuuming or working with the arms elevated and away from the body), or by levered postures (eg, bending forward).[18, 26]Pain is reduced when the spine is balanced by multidirectional forces (eg, walking or constantly changing positions) or when the spine is unloaded (eg, reclining). Mechanical conditions of the spine, including disk disease, spondylosis, spinal stenosis, and fractures, account for up to 98% of LBP cases, with the remaining ones due to systemic, visceral, or inflammatory disorders.[1]Mechanical versus nonmechanical spinal disorders

Mechanical syndromes

Diskal and facet motion segment degeneration

Muscular pain disorders (eg, myofascial pain syndrome)

Diskogenic pain with or without radicular symptoms

Radiculopathy due to structural impingement

Axial or radicular pain due to a biochemical or inflammatory reaction to spinal injury

Motion segment or vertebral osseous fractures

Spondylosis with or without central or lateral canal stenosis

Macroinstability or microinstability of the spine with or without radiographic hypermobility or evidence of subluxation

Nonmechanical syndromes

Neurologic syndromes

Myelopathy or myelitis from intrinsic/extrinsic structural or vascular processes

Lumbosacral plexopathy (eg, diabetes, vasculitis, malignancy)

Acute, subacute, or chronic polyneuropathy (eg, chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, diabetes)

Mononeuropathy, including causalgia (eg, trauma, diabetes)

Myopathy, including myositis and various metabolic conditions

Spinal segmental, lumbopelvic, or generalized dystonia

Systemic disorders

Primary or metastatic neoplasms

Osseous, diskal, or epidural infections

Inflammatory spondyloarthropathy

Metabolic bone diseases, including osteoporosis

Vascular disorders (eg, atherosclerosis, vasculitis)

Referred pain

Gastrointestinal disorders (eg, pancreatitis, pancreatic cancer, cholecystitis)

Cardiorespiratory disorders (eg, pericarditis, pleuritis, pneumonia)

Disorders of the ribs or sternum

Genitourinary disorders (eg, nephrolithiasis, prostatitis, pyelonephritis)

Thoracic or abdominal aortic aneurysms

Hip disorders (eg, injury, inflammation, or end-stage degeneration of the joint and associated soft tissues [tendons, bursae, ligaments])

Although acute LBP has a favorable prognosis, the effect of cLBP and its attendant disability on society is tremendous. Unlike acute LBP, cLBP serves no biological purpose. It is a disorder that evolves in a complex milieu influenced by endogenous and exogenous factors that alter the individual's productivity more than the initiating pathological dysfunction would have.

If diagnostic studies do not reveal a structural cause, physicians and patients alike question whether the pain has a psychological, rather than physical, cause. Physical and nonphysical factors, interwoven in a complex fashion, influence the transition from acute to chronic LBP. The identification of all contributing physical and nonphysical factors enables the treating physician to adopt a comprehensive approach with the greatest likelihood of success.

Epidemiology

LBP is the most expensive, benign condition in industrialized countries.[7]Experts have estimated that approximately 80% of Americans will experience LBP during their lifetimes.[7, 27, 28]The annual prevalence of LBP is 15-45% with a point prevalence of approximately 30%.[2]Sixty percent of those who suffer from acute LBP recover in 6 weeks and up to 80-90% recover within 12 weeks; however, the recovery of the remaining patients with LBP is less certain.[2]About 2% of American workers suffer compensable back injuries each yeara staggering 500,000 cases. LBP accounts for 19% of all workers' compensation claims in the United States. According to the Bureau of Labor and Statistics, metal workers generate 76% of all claims of back strain and/or sprains. Jobs that require heavy manual labor and material-handling activities account for more than half of all back pain reports. Injuries to the back are highest among truck drivers, operators of heavy equipment, and construction workers. From 1971-1981, the number of Americans disabled by LBP grew 14 times faster than the general population. The resultant disability in Western society has reached epidemic proportions, with enormous socioeconomic consequences.

An estimated 4.1 million Americans had symptoms of an intervertebral disk disorder between 1985 and 1988, with an annual prevalence of about 2% in men and 1.5% in women. A study of 295 Finnish concrete workers aged 15-64 years revealed that 42% of men, and as many as 60% of the men aged 45 years or older, reported having sciatica. When interviewed approximately 5 years later, the lifetime prevalence had increased from 42% to 59%.

Sciatica due to lumbar intervertebral disk herniations usually resolves with conservative treatment. However, it leads to surgery more often than back pain alone. In a published review of more than 15,000 disk operations, the most common surgical level was L4-5 (49.8%), followed by L5-S1 (46.9%); only 3.4% were performed at levels higher than these. Surgical treatment for lumbar diskogenic syndromes is most common in the United States, where the estimated rate is at least 40% higher than that in other countries and more than 5 times higher than rates in Scotland and England.

Risk Factors

LBP is most prevalent in industrialized societies. Genetic factors that predispose persons of specific ethnicity or race to this disorder have not been clearly identified with respect to mechanical, diskogenic, or degenerative causes. Men and women are affected equally, but in those older than 60 years, women report LBP symptoms more often than men. The incidence of LBP peaks in middle age and declines in old age when degenerative changes of the spine are universal. Sciatica usually occurs in patients during the fourth and fifth decades of life; the average age of patients who undergo lumbar diskectomy is 42 years.

Epidemiological data suggest that risk factors, including extreme height, cigarette smoking, and morbid obesity, may predispose an individual to back pain. However, research studies have not clearly demonstrated that height, weight, or body build are directly related to the risk of back injury. Weakness of the trunk extensor muscles, compared with flexor strength, may be a risk factor for sciatica. Fitness may be correlated with the time to recovery and return to work after LBP; however, in prospective studies controlled for age, isometric lifting strength and the degree of cardiovascular fitness were not predictive of back injury.

Occupational risk factors are difficult to define because exposures to specific causative influences are unclear, mechanisms of injury may be confusing, and the research supporting these findings is variable and conflicting for most environmental risks. Furthermore, job dissatisfaction, work conditions, legal and social factors, financial stressors, and emotional circumstances heavily influence back disability. Although many experts agree that heavy physical work, lifting, prolonged static work postures, simultaneous bending and twisting, and exposure to vibration may contribute to back injuries, the medical literature provides conflicting support for most of these proposed risk factors.

Pathophysiology

Degenerative cascade

The lumbar spine forms the caudal flexible portion of an axial structure that supports the head, upper extremities, and internal organs over a bipedal stance. The sacrum forms the foundation of the spine through which it articulates with the sacroiliac joints to the pelvis. The lumbar spine can support heavy loads in relationship to its cross-sectional area. It resists anterior gravitational movement by maintaining lordosis in a neutral posture.

Unlike the thoracic spine, the lumbar spine is unsupported laterally and has considerable mobility in both the sagittal and coronal planes. The bony vertebrae act as specialized structures to transmit loads through the spine. Parallel lamellae of highly vascularized cancellous bone form trabeculae, which are oriented along lines of biomechanical stress and encapsulated in a cortical shell. Vertebral bodies progressively enlarge going down because gravitational loads increase from the cephalic to the caudal segments. Bony projections from the lumbar vertebrae, including the transverse processes and spinous processes, maintain ligamentous and muscular connections to the segments above and below them.

The intervertebral disk is composed of the outer annulus fibrosis and the inner nucleus pulposus. The outer portion of the annulus inserts into the vertebral body and accommodates nociceptors and proprioceptive nerve endings. The inner portion of the annulus encapsulates the nucleus, providing the disk with extra strength during compression. The nucleus pulposus of a healthy intervertebral disk constitutes two thirds of the surface area of the disk and supports more than 70% of the compressive load.

The nucleus is composed of proteoglycan megamolecules that can imbibe water to a capacity approximately 250% of their weight. Until the third decade of life, the gel of the inner nucleus pulposus is composed of approximately 90% water; however, the water content gradually diminishes over the next 4 decades to approximately 65%. Nutrition to the inner annulus fibrosis and nucleus pulposus depends on the diffusion of water and small molecular substances across the vertebral endplates because only the outer third of the annulus receives blood supply from the epidural space.

Repeated eccentric and torsional loading and recurrent microtrauma result in circumferential and radial tears in the annular fibers. Some annular tears may cause endplate separation, which results in additional loss of nuclear nutrition and hydration. The coalescence of circumferential tears into radial tears may allow nuclear material to migrate out of the annular containment into the epidural space and cause nerve root compression or irritation.

Throughout the first 2 decades, 80-90% of the weight of the lumbar spine's trijoint complex is transmitted across the posterior third of the disk; however, as disk height decreases and the biomechanical axis of loading shifts posteriorly, the posterior articulations (ie, facet joints) bear a greater proportion of the weight distribution. Bone growth (in the form of new osteophytes) compensates for this increased biomechanical stress to stabilize the trijoint complex.

Over time, hypertrophy of the facets and bony overgrowth of the vertebral endplates contribute to progressive foraminal and central canal narrowing. In addition to relative thickening of the ligament flavum and disk herniation, these changes contribute to a reduction of the anteroposterior canal diameter and foraminal patency with neural compression. Spinal stenosis reaches a peak later in life and may produce radicular, myelopathic, or vascular syndromes such as pseudoclaudication and spinal cord ischemia.

LBP is most common in the early stages of disk degeneration, in what Kirkaldy-Willis called the stabilization phase. Impaired healing of the intervertebral disk due to its poor peripheral blood supply has been proposed as a possible explanation for the divergent behavior of this structure, which can produce chronic nociception. Also, the discovery of the biochemical factors that are responsible for causing increased sensitization of the disk and other pain-sensitive structures within the trijoint construct will eventually explain the mechanism of this discrepancy.

Characteristics of Pain-Sensitive Structures

Diskogenic pain

Many studies have demonstrated that the intervertebral disk and other structures of the spinal motion segment can cause pain.

Kuslich et al used regional anesthesia in 193 patients who were about to undergo lumbar decompressive surgery for disk herniation or spinal stenosis.[29]Pain was elicited by using blunt surgical instruments or an electrical current of low voltage in 30% of patients who had stimulation of the paracentral annulus fibrosis and in 15% with stimulation of the central annulus fibrosis. However, it is unclear why mechanical back pain syndromes commonly become chronic, with pain persisting beyond the normal healing period for most soft-tissue or joint injuries in the absence of nonphysical or operant influences.

In 1987, Mooney proposed that this LBP chronicity was best explained by a tissue component of the spine that obeyed physiological rules different from those of other connective tissues in the body.[30]This divergent behavior is best illustrated in the intervertebral disk with its composition of large, unique, water-imbibing proteoglycan molecules. During adulthood, these large molecules break into small molecules that bind less water. Repair by means of proteoglycan synthesis is slow. Fissuring and disruption of the annular lamellae further exacerbate molecular breakdown and the dehydration of the disk. Arterial blood supply to the peripheral one third of the outer annulus is meager and inadequate to prevent subsequent internal degeneration. The annulus and nucleus pulposus are similarly compromised, as they receive nutrition only by means of diffusion through adjacent vertebral endplates. Although sluggish healing of the intervertebral disk may partially account for the tendency of a spinal lesion to lead to chronicity, a direct concordance between structural degeneration and spinal pain does not exist.

Recent elucidation of biochemical behaviors and neurophysiological factors affecting the disk and other regional pain-sensitive tissues may account for this discrepancy. In humans, painful disks have a lower pH than nonpainful disks. Also, experimental lowering of the pH in animal models induced pain-related behaviors and hyperalgesia. Diskography of canine disks that were normally or experimentally deformed seemed to show increased concentrations of neuropeptides, such as substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) in the dorsal root ganglion (DRG), implicating their possible role in the transmission or modulation of pain. SP probably modulates initial nociceptive signals received in the gray matter of the dorsal spinal cord.

Somatostatin is another neuropeptide found in high concentrations in the dorsal gray matter of the spinal cord. Somatostatin is released from the DRG after noxious thermal stimulation and likely plays a role in pain transmission and in producing neurogenic inflammation. Therefore, the release of neuropeptides like SP, VIP, and CGRP may occur in response to noxious biochemical forces and environmental factors (eg, biomechanical stress, microtrauma, vibration), stimulating the synthesis of inflammatory agents (eg, cytokines, prostaglandin E2) and degradative enzymes (eg, proteases, collagenase). These factors cause progressive deterioration of the motion segment structures, especially the intervertebral disk.

Inflammatory factors may be responsible for pain in some cases in which epidural steroid injections provide relief. Corticosteroids inhibit the production of arachidonic acid and its metabolites (prostaglandins and leukotrienes), inhibiting phospholipase A2 (PLA2) activity. PLA2 levels, which play a role in inflammation, are elevated in surgically extracted samples of human herniated disks. Furthermore, PLA2 may play a dual role, inciting disk degeneration and sensitizing annular nerve fibers. Afferent nociceptors in nerve roots may be sensitive to various proinflammatory mediators, which are inhibited by corticosteroids, such as prostanoids produced from arachidonic acid and released from cell membrane phospholipids by PLA2.

Research suggests that proinflammatory cytokines may also contribute to diskogenic pain by sensitizing nociceptors and disk degeneration by suppressing proteoglycan synthesis and increasing diskal matrix degradation. Cytokines are produced in response to neural injury in the CNS and may play a role in spinal neural hypersensitization and chronic neuropathic pain. Cytokines known to play a role in nociception include nerve growth factor, interleukin (IL)-1, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-).

Corticosteroids can inhibit activity of TNF-, which induces IL-1 and prostaglandin E2production. Once released, these substances contribute to early and late effects of the inflammatory process and stimulate nociception. A nociceptive role for nitric oxide (NO) in diskogenic pain syndromes is under investigation. NO levels are elevated in human disk herniations and when the hydrostatic pressure of the disk is increased due to biomechanical stressors. NO inhibits proteoglycan synthesis in cells in the nucleus pulposus, leading to proteoglycan loss, reduced water content, and disk degeneration.

Neurotransmitters and biochemical factors may sensitize neural elements in the motion segment so that the normal biomechanical stresses induced by previously asymptomatic movements or lifting tasks cause pain. Furthermore, injury and the subsequent neurochemical cascade may modify or prolong the pain stimulus and initiate the degenerative and inflammatory changes described above, which mediate additional biochemical and morphologic changes. Whether the biochemical changes that occur with disk degeneration are the consequence or cause of these painful conditions is unclear. However, chemical and inflammatory factors may create the environmental substratum on which biochemical forces cause axial or limb pain with various characteristics and to various degrees.

Radicular pain

The pathophysiology of spinal nerve root or radicular pain is unclear. Proposed etiologies include neural compression with axonal dysfunction, ischemia, inflammation, and biochemical influences. Spinal nerve roots have unique properties that may explain their proclivity toward producing symptoms. Unlike peripheral nerves, spinal nerve roots lack a well-developed intraneural blood-nerve barrier, and this lack makes them more susceptible to symptomatic compression injury.

Increased vascular permeability caused by mechanical nerve-root compression can induce endoneural edemas. Furthermore, elevated endoneural fluid pressure due to an intraneural edema can impede capillary blood flow and cause intraneural fibrosis. Also, spinal nerve roots receive approximately 58% of their nutrition from surrounding cerebral spinal fluid (CSF). Perineural fibrosis, which interferes with CSF-mediated nutrition, renders the nerve roots hyperesthetic and sensitive to compressive forces.

Research has elucidated several vascular mechanisms that can produce nerve-root dysfunction. Experimental nerve-root compression showed that venous blood flow can be stopped at low pressures, ie, 5-10 mm Hg. The occlusion pressure for radicular arterioles is substantially higher than this, approximating the mean arterial blood pressure and showing a correlation with systolic blood pressure; this factor increases the potential for venous stasis.

Some investigators postulate that venous-then-capillary stasis causes some congestion that, in turn, may induce symptomatic nerve root syndromes. Nerve root ischemia or venous stasis may also generate pathological biochemical changes that cause pain, unlike the progressive sensory-then-motor dysfunction typically seen with peripheral nerve compression. Studies of ischemia experimentally induced with low-pressure nerve root compression demonstrated that compensatory nutrition from CSF diffusion is probably inadequate when epidural inflammation or fibrosis is present. Rapid-onset neural and vascular compromise is more likely than a slow or gradual mechanical deformity to produce symptomatic radiculopathy.

Research has revealed other possible causative mechanisms for symptomatic radiculopathy. A 1987 animal study showed that autologous nucleus pulposus placed in the epidural space of dogs produced a marked epidural inflammatory reaction that did not occur in the comparison group, which received saline injections. Similar studies have shown that myelin-related and axonal injury to nerve roots exposed to autologous nucleus pulposus demonstrate reduced nerve conduction velocities.

However, recent studies have demonstrated that experimental exposure of nerve roots to degenerative nucleus pulposus and annulus fibrosis does not produce the same dysfunctional neural changes; therefore, viable cells of the nucleus pulposus are necessary to induce localized neural dysfunction and generate algogenic agents, such as metalloprotease (eg, collagenase, gelatinase), IL-6, and prostaglandin-E2.

Other biochemical substances, including TNF, have been implicated as causes. TNF increases vascular permeability and appears to be capable of inducing neuropathic pain. When injected into nerve fascicles, TNF produces changes similar to those seen when nerve roots are exposed to the nucleus pulposus. In addition, a still-unanswered question is whether an autoimmune response occurs when the nucleus pulposus is exposed to the systemic circulation, because it is usually sequestered by the annulus fibrosis and, thus, the immune system may not recognize it as normal. Indeed, research to date suggests that the cause of symptomatic radiculopathy is more complex than just neural dysfunction due to structural impingement.

Facet joint pain

The superior and inferior articular processes of adjacent vertebral laminae form the facet or zygapophyseal joints, which are paired diarthrodial synovial articulations that share compressive loads and other biomechanical forces with the intervertebral disk. Like other synovial joints, the facets react to trauma and inflammation by manifesting pain, stiffness, and dysfunction with secondary muscle spasm leading to joint stiffness and degeneration. This process is borne out, as previously described, through the degenerative cascade of the trijoint complex. Numerous radiological and histological studies have shown that diskal and facet degeneration are linked and that, over time, degeneration of the segment leads to osteoarthritis of the facets.

Studies of provocative intra-articular injection techniques demonstrated local and referred pain into the head and upper extremities from cervical facets, into the upper midback and chest wall from thoracic facets, and into the lower extremity from the lumbar facets. The fibrous capsule of the facet joint contains encapsulated, unencapsulated, and free nerve endings.

Immunohistochemical studies have demonstrated nerve fibers containing neuropeptides that mediate and modulate nociception (eg, SP, CGRP, VIP). SP-filled nerve fibers have been found in subchondral bone and degenerative lumbar facets subjected to aging and cumulative biomechanical loading. In fact, SP levels are correlated with the severity of joint arthritis. The infusion of SP into joints with mild disease reportedly accelerates the degenerative process. Furthermore, these chemicals and inflammatory mediators have been linked to proteolytic and collagenolytic enzymes that cause osteoarthritis and degradation of the cartilaginous matrix. Therefore, evidence of nociceptive afferents and the presence of algogenic neuropeptides, such as SP and CGRP, in facets and periarticular tissues support a role for these structures as spinal pain generators. Clinical research has demonstrated facet pain in 54-67% of patients with neck pain, 48% of patients with thoracic pain, and 15-45% of patients with LBP.

Sacroiliac pain

The sacroiliac joint is a diarthrodial synovial joint that receives its primary innervation from the dorsal rami of the first 4 sacral nerves. Arthrography or injection of irritant solutions into the sacroiliac joint provokes pain with variable local and referred pain patterns into regions of the buttock, lower lumbar area, lower extremity, and groin. As determined by using a variety of blocking techniques, the reported prevalences of sacroiliac pain have been widely variable (2-30%) in patients evaluated for chronic LBP.

Muscular pain

Pain receptors in muscle are sensitive to a variety of mechanical stimuli, including pressure, pinching, cutting, and stretching. Pain and injury occur when the musculotendinous contractual unit is exposed to single or recurrent episodes of biomechanical overloading. Injured muscles are usually abnormally shortened, with increased tone and tension due to spasm or overcontraction. Injured muscles often meet the diagnostic criteria for myofascial pain (MP) syndrome, a condition that Drs. Janet Travell and David Simons originally described.

MP is characterized by muscles that are in a shortened or contracted state, with increased tone and stiffness, and that contain trigger points (TrPs). TrPs are tender, firm, 3- to 6-mm nodules that are identified on palpation of the muscles. TrP palpation provokes radiating, aching pain into localized reference zones. Mechanical stimulation of the taut band, a hyperirritable spot in the TrP, by needling or rapid transverse pressure often elicits a localized muscle twitch.

Sometimes, TrP palpation can elicit a jump sign, an involuntary reflex, or flinching disproportionate to the palpatory pressure applied. MP may become symptomatic as a result of direct or indirect trauma, exposure to cumulative and repetitive strain, postural dysfunction, or physical deconditioning. MP can occur at the site of tissue damage or as a result of radicular and other neuropathic disorders at sites where pain is referred. Muscles affected by neuropathic pain may be injured due to prolonged spasm, mechanical overload, or metabolic and nutritional shortfalls.

The pathogenesis of MP and TrPs remains unproven. To date, research suggests that myofascial dysfunction with characteristic TrPs is a spinal segmental reflex disorder. Animal studies have showed that TrPs can be abolished by transecting efferent motor nerves or infusing lidocaine; however, spinal transection above the level of segmental innervation of a TrP-containing muscle does not alter the TrP response. Simons postulates that abnormal, persistently increased, and excessive acetylcholine release at the neuromuscular junction generates sustained muscle contraction and a continuous reverberating cycle. This cycle has been postulated to result in painful and dysfunctional extrafusal muscle contraction that forms the basis for MP and possibly the actual structural substrate of the TrP.

Neurophysiology of spinal pain

Nociception is the neurochemical process whereby specific nociceptors convey pain signals through peripheral neural pathways to the central nervous system (CNS). Acute tissue damage to the spinal motion segment and associated soft tissues activates these pathways. When the peripheral source of pain persists, intrinsic mechanisms that reinforce nociception influence the pain. The nervous system can enhance a pain stimulus generated by tissue damage to levels far greater than any threat it signifies to the human organism; this is a common clinical scenario in cases of chronic spinal pain.

Noxious mechanical, thermal, and chemical stimuli activate peripheral nociceptors that transmit the pain message through lightly myelinated A-delta fibers and unmyelinated C-fibers. Nociceptors are present in the outer annular fibrosis, facet capsule, posterior longitudinal ligament, associated muscles, and other structures of the spinal motion segment. Peripheral transmission of pain stimuli leads to the release of excitatory amino acids, such as glutamine and asparagine, which then act onN-methyl-D-aspartic acid (NMDA) receptors, causing the release of the neuropeptide SP. Neuropeptides such as SP, CGRP, and VIP are transported to the endings of nociceptive afferents, which inflammation and other algogenic mechanisms sensitize. Thereafter, the affected nociceptors respond to mild or normal sensory stimuli, such as a light touch or temperature change (allodynia).

Algogenic substances that are typically involved in tissue damage and that can induce peripheral transduction include potassium, serotonin, bradykinin, histamine, prostaglandins, leukotrienes, and SP. Transduction leads to transmission, which is the conduction of afferent pain signals to the DRG and dorsal horn of the spinal cord. The DRG contains the cell bodies of various primary afferent nociceptors, including for the neuropeptides SP, VIP, and CGRP. The DRG is mechanically sensitive and capable of independent pain transduction, transmission, and modulation. Transduction is the process whereby noxious afferent stimuli are converted from chemical to electrical messages in the spinal cord that travel cephalad to the brainstem, thalamus, and cerebral cortex.

Nociceptive modulation first occurs in the dorsal horn, where nociceptive afferents converge to synapse on a single wide dynamic range (WDR) neuron. WDR neurons respond with equal intensity regardless of whether the neural signal is noxious or an exaggerated nonpainful stimuli (hyperalgesia). Hyperalgesia and allodynia initially develop at the injury site; however, when peripheral and central sensitization occur by means of WDR neural activity and central processing, the area of pain expands beyond the initial more-limited region of focal tissue pathology.

Finally, a phenomenon termedwind-upresults from the repetitive activation of C-fibers sufficient to recruit second-order neurons that respond with progressively increasing magnitude; NMDA receptor antagonists can block this effect. Wind-up contributes to central sensitization, including hyperalgesia, allodynia, and persistent pain. These nociceptive mechanisms, which reinforce the pain signal, frequently recruit the sympathetic nervous system. Elevated norepinephrine levels in injured areas increase pain sensitivity by means of regional vasomotor and sudomotor changes. Also, higher acetylcholine levels can augment ongoing local and regional involuntary muscle contraction and spasm.

Evolutionary Mechanisms in Chronic LBP

Chronic LBP (cLBP) is not the same as acute LBP that persists for a greater duration. Usually 6-7 weeks is sufficient for healing to occur in most soft-tissue or joint injuries; however, 10% of LBP injuries do not resolve in this period. The evolution of cLBP is complex, with physiological, psychological, and psychosocial influences. These influences can be divided into 3 major categories, with subcategories, as follows:

Neurophysiological mechanisms

Peripheral

Peripheral to central

Psychological mechanisms

Behavioral

Cognitive-affective

Psychophysiological

Barriers to recovery

Medical and surgical

Physical

Psychological

Neuropsychological

Social

Neurophysiological mechanisms

Peripheral mechanisms may reinforce nociception when the source of pain persists. If an ongoing pathological condition causes the peripheral pain stimulus, continuous nociception may induce repetitive stimulation and sensitization of pain receptors and nerve fibers so that they adversely respond to even mild or normal sensory stimuli (ie, allodynia). Furthermore, the liberation of algogenic and other substances from damaged tissues may induce changes in the microenvironment by means of neuroactive, biochemical, inflammatory, or vasoactive effects that activate or increase the sensitivity of nociceptors.

Peripheral-to-central processing may also modify nociception. Persistent tissue damage may stimulate afferent nerve fibers that project to internuncial neurons in the spinal cord and thereby set up neuronal loops of continuous, self-sustaining abnormal reverberating nociceptive activity. Peripheral inhibition, a mechanism for reducing the intensity of an afferent pain signal, may be impaired owing to persistently malfunctioning or diseased large peripheral myelinated fibers, which normally dampen nociception (eg, peripheral neuropathy, epidural scarring, chronic herniated disk material).

Ectopic impulse generation is a theoretical mechanism Wall and Gutnick proposed.[31]Damaged sensory nerves, affected by conditions such as neuromata or demyelinating lesions in peripheral nerves, produce aberrant signals. Deafferentation hypersensitivity also purportedly causes abnormal and chronic nociceptive firing patterns.

CNS bias of the signal may occur in the spinal cord, brainstem reticular formation, or cortex. The brainstem reticular formation acts to direct the attention of the CNS toward or away from central and peripheral stimuli. Depending on the degree of focus, or the lack thereof, the transmission of pain signals may be either enhanced or inhibited. Furthermore, cortical influences, such as cognitive and affective disorders, may affect the intensity of the processed pain signal.

Psychological mechanisms

Psychological manifestations are 3-fold; they include behavioral, cognitive-affective, and psychophysiological mechanisms. Guarded movements, nonverbal and verbal expressions of pain, and inactivity are called pain behaviors. Normal healthy behavior patterns may become extinguished when these verbal and nonverbal pain behaviors are reinforced by environmental factors.

Cognitive-affective mechanisms often contribute to the perception of chronic pain. Pain complaints are common in depressed individuals, and patients with chronic pain frequently become depressed. Depression acts though biochemical processes similar to those that operate in chronic pain; this may enhance symptoms through a synergistic relationship. Patients with pain who are depressed may illogically interpret and distort life experiences, further complicating the feasibility of treatment or employment.

Psychophysiological mechanisms naturally triggered by pain and injury can lead to generalized muscle overactivity, increased fatigue, and other pain problems (eg, tension myalgia, headache). The emotional stress that pain induces tends to heighten norepinephrine activity and the general activity of the sympathetic nervous system, which may further amplify nociception by means of peripheral or central mechanisms.

Barriers to recovery

Barriers to recovery may be premorbid, result from traumatic injury, or develop over time as a result of psychological and environmental influences. These barriers strongly influence chronicity and the patient's prognosis. For example, medical problems, such as diabetes or heart disease, may make the patient a poor candidate for rehabilitation or surgery. Failed back surgery may create permanent physical and psychological obstacles.

Patients differ in their inherent capacity to exercise. Deconditioning syndrome, a term Mayer coined, is caused by prolonged reduction of physical activity due to cLBP. This syndrome is associated with a gradual reduction in muscle strength, joint mobility, and cardiovascular fitness, which over time may become a self-sustaining and independent component of the individual's musculoskeletal illness.

Preexisting psychological factors may combine with lower back injuries to create a pain syndrome with predominantly psychiatric features. Psychiatric interviews of 200 patients with cLBP entering a functional restoration (FR) program revealed that 77% met lifetime diagnostic criteria for psychiatric syndromes, even when the category of somatoform pain disorder was excluded. In addition, 51% met the criteria for at least 1 personality disorder.

Psychological barriers to recovery include those listed below.

Premorbid factors

Depression, dysthymia

Predisposition toward somatoform pain disorder

Psychoactive substance-abuse disorder

Personality disorder or traits thereof

Anxiety disorders including panic disorder

Childhood sexual abuse

Cognitive process

Psychosis, delusional pain

Traumatic factors

Anxiety/panic

Fear

Psychophysiological response

Loss of control

Abnormal dependence

Posttraumatic factors

Anxiety, panic

Depression

Posttraumatic stress disorder

Anger/hostility

Iatrogenic substance abuse

Somatoform pain disorder

Symptom magnification

Increasing time since injury

Disability mindset

Personality disorders or related traits often affect the prognosis. People with borderline personalities may acquire pain as a method for structuring an otherwise empty existence, whereas patients who are narcissistic may acquire pain and seek medical attention as a way of preventing more serious illness. Those with an antisocial personality are often exploitative and prone to complications, and they may easily adopt game-playing roles. Patients with somatizing and hypochondriacal conditions are most likely to develop pain as a symptom and least likely to respond to treatments aimed at a presumed organic cause. Individuals with depression are prone to chronic pain or to have pain as a symptom. Other personality disorders or disorders that may influence chronic pain include the paranoid, passive-aggressive, and avoidant conditions.

Previous learning and role models also affect the patient's prognosis and treatment outcome. An individual's cognitive or attribution style (eg, the patient's tendency to catastrophize, overgeneralize, personalize, or selectively attend to negative aspects of the pain experience) heavily influence prognosis and treatment outcomes. The physical and emotional trauma that occurred during the injury or that was encountered during the ordeal of convalescence may contribute to the psychosocial milieu and create a host of emotional responses, including anxiety and fear.

Psychophysiological responses may be reinforced and include nightmares, palpitations, diaphoresis, headaches, dizziness, irritability, and fatigue. Patients are often overwhelmed and have feelings of abnormal dependence. They perceive a loss of control and look to their physician, attorney, or family for guidance. Some advisors may be oversolicitous or encourage compensation-seeking or litigation, creating further barriers to recovery.

Enduring prolonged pain also may cause emotional disturbances. Depression has already been mentioned as a common partner to chronic pain and is enhanced by the loss of physical function, low self-esteem, loss of employment, and financial insecurity. Heightened anxiety may occur secondary to continued pain and the associated life disruption. Fear of injury and panic symptoms may also enhance anxiety and complicate the person's recovery. Anger or hostility directed at the workplace or perceived ineffective medical care may hinder communication with physicians, employers, family, and friends. As the length since the injury increases, the aggregation of posttraumatic emotions becomes increasingly complex; avoidance learning and deactivation further complicate the situation.

As these barriers accumulate, the probability of a poor prognosis rises. Neuropsychological factors may preexist or come into effect due to the injury. Limited cognitive function, either premorbid or from brain injury, may limit the patient's capacity to make decisions or succeed in a rehabilitation program.

Neuropsychological barriers to recovery include the following:

Intelligence

Brain injury

Dementia or other organic mental syndromes

Environmental and social influences may play the strongest role in determining the patient's prognosis for chances of recovery. Job dissatisfaction or conflict is a key predictor of chronic LBP with disability. Compensated unemployment may reinforce chronicity in these cases. Family, financial, and legal issues also affect chronicity. A patient with chronic LBP may be unable to return to a previous job that was strenuous or involved heavy lifting and may be poorly equipped to pursue alternative vocational options because of a lack of education. Older individuals may have reduced capacity for work and less vocational potential; therefore, loss of compensation becomes an overriding issue.

Social barriers to recovery include the following:

Job dissatisfaction or conflict

Compensated unemployment as a disincentive

Family or spousal dynamics

Perception of the norm, ie, family history

Legal influences

Financial security

Limited education or vocational potential

Age-related factors

Clinical Evaluation

History

In most cases, chronic LBP has been investigated with the appropriate physician evaluation and perhaps imaging studies. Characterization of the pain as mechanical is a primary goal when a history is obtained from a patient with cLBP and sciatica. Mechanical or activity-related spinal pain is most often aggravated by static loading of the spine (eg, prolonged sitting or standing), long-lever activities (eg, vacuuming or working with the arms elevated and away from the body), and levered postures (eg, forward bending of the lumbar spine). Pain is reduced when multidirectional forces balance the spine eg, walking or constantly changing positions) and when the spine is unloaded (eg, reclining). Patients with mechanical LBP often prefer to lie still in bed, whereas those with a vascular or visceral cause are often found writhing in pain, unable to find a comfortable position.

Unrelenting pain at rest should suggest a serious cause, such as cancer or infection. Imaging studies and a blood workup are usually mandatory in these cases and in cases with progressive neurological deficits. Other historical, behavioral, and clinical signs that should alert the physician to a nonmechanical etiology requiring diagnostic evaluation are outlined below.

Diagnostic red flags

Pain unrelieved by rest or any postural modification

Pain unchanged despite treatment for 2-4 weeks

Writhing pain behavior

Colicky pain or pain associated with a visceral function

Known or previous cancer

Fever or immunosuppressed status

High risk for fracture (eg, older age, osteoporosis)

Associated malaise, fatigue, or weight loss

Progressive neurological impairment

Bowel or bladder dysfunction

Severe morning stiffness as the primary complaint

Patients unable to ambulate or care for self

Nonphysiological or implausible descriptions of pain may provide clues that operant or other psychosocial influences coexist.

Prognostic red flags

Nonorganic signs and symptoms

Dissociation between verbal and nonverbal pain behaviors

Compensable cause of injury

Out of work, disabled, or seeking disability

Psychological features, including depression and anxiety

Narcotic or psychoactive drug requests

Repeated failed surgical or medical treatment for LBP or other chronic illnesses

Physical Examination

Physical examination is important to confirm a mechanical or benign cause for the patient's LBP. Observations of verbal and nonverbal behaviors suggesting symptom magnification should be noted. Inspection of the spine requires the patient to disrobe. Open-back gowns give the physician only 1 view of the spine; therefore, swimming attire is often appropriate for complete, 360 inspection. Leg-length discrepancy and pelvic obliquity, scoliosis, postural dysfunction with forward-leaning head and shoulders, or accentuated kyphosis should be noted. Physicians' preferences vary with regard to the importance of testing range of motion; however, just asking the patient to bend forward often enables the most worthwhile observations.

The patient is asked to drop his or her head and shoulders forward and then move slowly into forward bending. Normal forward bending is revealed when the patient recruits from each cephalic segment to the level below, and so on, progressing from the cervical spine through the thoracic and lumbar region, where flexion of the hips completes the excursion into full flexion. Patients with clinically significant mechanical back pain or lumbar segmental instability usually stop cephalic-to-caudal segmental recruitment on reaching the thoracolumbar junction, or sometimes the involved lumbar level. To continue forward bending, they then contract their lumbar muscles to brace the mechanically compromised segment and then continue recruitment in a reverse direction, beginning with motion through the hips, then proceeding cephalad, level to level, completing the excursion of the spine to the erect posture.

In cases of severe mechanical back pain and segmental instability with regional muscular spasm, the patient often reports an inability to perform any flexion below a thoracic spinal level. Any soft-tissue abnormalities and tenderness to palpation should be recorded. Palpation of lumbar paraspinal, buttock, and other regional muscles should be performed early in the examination. The examiner should palpate and note areas with superficial and deep-muscle spasm, and he or she should identify TrPs and small, tender nodules in a muscle that elicit characteristic regional referred pain.

Dissociation of physical findings from physiological or anatomical principles is the key with patients in whom psychological factors are suspected to be influential. Examples of this phenomenon include nondermatomal patterns of sensory loss, nonphysiological demonstrations of weakness (give-way weakness when not caused by pain, or ratchety weakness related to simultaneous agonist and antagonist muscular contraction), and dissociation between the lumbar spinal movements found during history-taking or counseling sessions from movements observed during examination.

The assessment of Waddell signs has been popularized as a physical examination technique to identify patients who have nonorganic or psychogenic embellishment of their pain syndrome. One of the examination techniques that Waddell proposed is simulated rotation of the hipsen massewith the lumbar spine without allowing for spinal rotation; this maneuver normally does not cause pain. Another is the application of light pressure on the head, which should also be painless. Likewise, gentle effleurage of superficial tissues is unlikely to cause pain. Other techniques include a striking dissociation between testing straight leg raising with the patient sitting versus supine and the examiner's discovery of nonphysiologic weakness and/or sensory deficits by the patient.

Straight leg raising with the patient supine should produce ipsilateral leg pain between 10 and 60 to be declared positive. Straight leg raising that produces pain in the opposite leg carries a high probability of disk herniation, and an investigation should be considered, especially if neurological evidence for radiculopathy is present. Nonspecific complaints, overtly excessive pain behavior, patient contraction of antagonist muscles that limit the examiner's testing, or tightness of buttock and hamstring muscles are commonly mistaken for positive results on straight leg raising.

Reverse straight leg raising may elicit symptoms of pain by inducing neural tension on irritated or compressed nerve roots in the mid-to-upper lumbar region. In addition, this maneuver helps the astute physician identify tightness of the iliopsoas muscle, which commonly contributes to chronic lumbar discomfort.

A neurological evaluation is performed to determine the presence or absence and levels (if present) of radiculopathy or myelopathy. Anatomical localization is determined by muscle and reflex testing combined with medical history details obtained during the interview and the absence of neurological symptoms or signs that implicate cerebral or brainstem involvement. Consistent myotomal weakness and sensory findings that seem to coincide with segmental radiculopathy or polyradiculopathies should not be ignored.

The neurologist should identify syndromes of the lower motor neurons versus the upper motor neurons and the level of spinal dysfunction. Hyperreflexia in caudal spinal levels may change to reduced or absent reflexes in the upper extremities, determining the radicular or spinal cord localization of dysfunction. Rectal examination is indicated in patients in whom myelopathy, especially cauda equina syndrome, is a diagnostic concern. The tone of the anal sphincter; presence or absence of an anal wink; and correlation with motor, sensory, and reflex findings are appropriate to determine in these cases.

When LBP persists beyond 3 months, into the chronic phase, appropriate clinical and diagnostic information supporting a benign or mechanical cause should be collected, if it has not been already. Also, a prompt physician evaluation, including reasonable radiographic, laboratory, and electrophysiological testing, is indicated in patients with persistent severe neurological deficit, intractable limb pain, suspected systemic illness, or changes in bowel or bladder control. The spectra of mechanical (or activity-related) and nonmechanical causes of LBP are outlined below.

Mechanical or activity-related causes of LBP

Diskal and segmental degeneration - May include facet arthropathy from osteoarthritis

Myofascial, muscle spasm, or other soft-tissue injuries and/or disorders

Disk herniation - May include radiculopathy

Radiographic spinal instability with possible fracture or spondylolisthesis - May be due to trauma or degeneration

Fracture of bony vertebral body or trijoint complex - May not reveal overt radiographic instability

Spinal canal or lateral recess stenosis

Arachnoiditis, including postoperative scarring

Differential diagnosis can include many neurological and systemic disorders, as well as referred pain from viscera or other skeletal structures such as the hip.

Disorders that may be associated with nonmechanical LBP

Neurological syndromes

Myelopathy from intrinsic or extrinsic processes

Lumbosacral plexopathy, especially from diabetes

Neuropathy, including the inflammatory demyelinating type (ie, Guillain-Barr syndrome)

Mononeuropathy, including causalgia

Myopathy, including inflammatory and metabolic causes

Dystonia, truncal or generalized central pain syndrome

Systemic disorders

Primary metastatic neoplasm, including myeloma

Osseous, diskal, or epidural infection

Inflammatory spondyloarthropathy

Metabolic bone disease, including osteoporosis

Vascular disorders such as atherosclerosis or vasculitis

Referred pain

Gastrointestinal disorders

Genitourinary disorders, including nephrolithiasis, prostatitis, and pyelonephritis

Gynecological disorders, including ectopic pregnancy and pelvic inflammatory disease

Abdominal aortic aneurysm

Hip pathology

Psychosocial factors that may influence LBP chronicity and disability

Compensable injury

Somatoform pain disorder

Psychiatric syndromes, including delusional pain

Drug-seeking

Abusive relationships

Seeking disability or out-of-work status

Diagnostic Strategies

As indicated in the last section, unrelenting pain at rest should generate suspicion of cancer or infection. The appropriate imaging study is mandatory in these cases and in cases of progressive neurological deficit. Plain anteroposterior and lateral lumbar spine radiographs are indicated for patients older than 50 years and for those with pain at rest, a history of serious trauma, or other potential conditions (eg, cancer, fracture, metabolic bone disease, infection, inflammatory arthropathy). The yield for discovering a serious condition with radiography outside these parameters is minimal, and the cost savings are substantial.

When LBP and sciatica persist into the subacute phase (pain lasting 6-12 wk), appropriate consultation and diagnostic imaging should be considered. Referring the patient to a physician with expertise in spinal disorders may be the most appropriate procedure for initial evaluation as opposed to relying on expensive diagnostic testing.

CT scanning is an effective diagnostic study when the spinal and neurological levels are clear and bony pathology is suspected.

MRI is most useful when the exact spinal and neurologic levels are unclear, when a pathological condition of the spinal cord or soft tissues is suspected, when postoperative disk herniation is possible, or when an underlying infectious or neoplastic cause is suspected.

Myelography is useful in elucidating nerve root pathology, particularly in patients with previous lumbar spinal surgery or with a metal fixation device in place. CT myelography provides the accurate visual definition to elucidate neural compression or arachnoiditis when patients have undergone several spinal operations and when surgery is being considered for the treatment of foraminal and spinal canal stenosis.

When leg pain predominates and imaging studies provide ambiguous information, clarification may be gained by performing electromyography (EMG), somatosensory evoked potential (SSEP) testing, or selective nerve root blocks. When the cause of sciatica is related to neural compression by bony or soft-tissue structures in the spinal canal, a surgical consultation should be considered. If the results of the diagnostic information are inadequate to explain the degree of neurological deficit, pain, and disability, a multidisciplinary evaluation may provide insight into the perpetuating physical and psychosocial factors (see image below).

Algorithm for the management of low back pain and sciatica.Nonoperative Treatment

Support for Nonsurgical Treatment

Doubt remains regarding the relative efficacy and cost-effectiveness of surgical versus nonsurgical treatment approaches. An important longitudinal study was performed by Henrik Weber, who randomly divided patients who had sciatica and confirmed disk herniations into operative and nonoperative treatment groups.[32]He found significantly greater improvement in the surgically treated group at 1-year follow-up; however, the 2 groups showed no statistically significant difference in improvement at 4 to 10 years.[32]Two prospective cohort studies compared the surgical and nonsurgical management of lumbar spinal stenosis and sciatica due to lumbar disk herniation.[33, 34]The results and conclusions were similar in both studies. For patients with severe symptoms, surgical treatment was associated with greater improvement and satisfaction. This distinction persisted, but diminished over time.[33, 34, 35]The recent and very ambitious Spinal Patient Outcomes Research Trial (SPORT) had been hoped to significantly clarify the surgical versus nonsurgical issues. So far, with data analyzed for 2- and 4-year follow-ups, finding definitive answers in this study is difficult, though they contain a large amount of interesting information. For disk herniation, the major conclusion at 4 years was that nonoperative treatment or surgery led to improvement in intervertebral disk herniation. But surgery may have a slight benefit.[36, 37]For spondylolisthesis, the 2- and 4-year as-treated analysis showed an advantage to surgical therapy.[38, 39]Likewise, for spinal stenosis, the 2-year analysis showed somewhat more improvement for surgery.[40]With regard to cost effectiveness, the surgical costs were rather high, though not completely out of the range of other medical treatments. For lumbar disk herniations, 1 quality-adjusted life year (Qaly) cost about $70,000. For stenosis and spondylolisthesis the costs per Qaly were $77,000 and $116,000, respectively.[41, 42]A significant general problem with the SPORT data is that there was so much switching between treatment groups that intention-to-treat analysis (the usual criterion standard) was impossible. Therefore as-treated analyses were used. As the SPORT analyses continue beyond the 2- to 4-years, additional information or more definitive changes between groups may be identified. But lack of an intention-to-treat analysis will probably complicate definitive conclusions. Hopefully, future studies and newer treatments may someday provide clearer answers.

The rationale for nonoperative treatment of diskal herniation has been supported by clinical and autopsy studies, which demonstrate that resorption of protruded and extruded disk material can occur over time.[43, 44]Other studies have correlated MRI or CT improvement with successful nonoperative treatment in patients who have lumbar disk herniations and clinical radiculopathy.[44, 45, 46]The greatest reduction in size typically occurred in patients with the largest herniations. Recent uncontrolled studies have shown that patients who have definite herniated disks and radiculopathy and satisfy the criteria for surgical intervention can be treated successfully with aggressive rehabilitation and medical therapy. Good to excellent results were achieved in 83% of cervical and 90% of lumbar patients.[47, 48]In general, nonoperative treatment can be divided into 3 phases based on the duration of symptoms. Primary nonoperative care consists of passively applied physical therapy during the acute phase of soft-tissue healing (< 6 wk). Secondary treatment includes spine care education and active exercise programs during the subacute phase between 6-12 weeks with physical therapydriven goals to achieve preinjury levels of physical function and a return to work. After 12 weeks, if the patient remains symptomatic, treatment focuses on interdisciplinary care using cognitive-behavioral methods to address physical and psychological deconditioning and disability that typically develops as a result of chronic spinal pain and dysfunction.[49]When spinal pain persists into the chronic phase, therapeutic interventions shift from rest and applied therapies to active exercise and physical restoration. This shift is primarily a behavioral evolution with the responsibility of care passed from doctor and therapist to patient.[18, 50]Bed rest should be used sparingly for chronic spinal pain to treat a severe exacerbation of symptoms. Therapeutic injections, manual therapy, and other externally applied therapies should be used adjunctively to reduce pain so that strength and flexibility training can continue. When spinal pain is chronic or recurrent, traction or modalities, such as heat and ice, can be self-administered by patients for flare-ups to provide temporary relief.[18, 50]Rational physical, medical, and surgical therapies can be selected by determining the relevant pathoanatomy and causal pain generators. Acute spinal injuries are first managed by the elimination of biomechanical stressors, using short-term rest, supplemented by physical and pharmacological therapies aimed directly at the nociceptive or neuropathic lesion(s).

The paradigm that best represents the elimination of activity or causative biomechanical loading is bed rest. Bed rest is usually considered an appropriate treatment for acute back pain. However, 2 days of bed rest for acute LBP has been demonstrated to be as effective as 7 days and resulted in less time lost from work.[51]Furthermore, prolonged bed rest can have deleterious physiological effects, leading to progressive hypomobility of joints, shortened soft tissues, reduced muscle strength, reduced cardiopulmonary endurance, and loss of mineral content from bone.[18, 7, 20]For these reasons and because inactivity may reinforce abnormal illness behavior, bed rest is usually avoided when treating chronic spinal conditions.[18, 7, 20]Oral Pharmacology

Rational pharmacology for the treatment of spinal pain is aimed at causative peripheral and central pain generators, determined by the types of pain under therapeutic scrutiny (eg, neuropathic and/or nociceptive), and modified additionally to deal with the evolving neurochemical and psychological factors that arise with chronicity. In general, the published research for evaluating the efficacy of medication in treating neck and back pain has demonstrated faulty methodology and inadequate patient/subject description.[52]However, medication continues to be used as adjunct to other measures because of anecdotal reports, perceived standards of care, and some supportive clinical research.

Some authors contend that analgesics like acetaminophen are a reasonable first step for the treatment of cLBP[53, 54], although others disagree and advocate its use only when treating acute LBP.[55]There is evidence that acetaminophen has a similar efficacy to nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with acute LBP; however, little direct evidence exists regarding the efficacy of acetaminophen in cLBP.[56]The possible beneficial effects of long-term acetaminophen use must be weighed against potential adverse hepatic and renal effects.[57]There is strong evidence that both traditional and cyclooxygenase-2-specific NSAIDs are more efficacious than a placebo for reducing LBP in the short term, although the effects tend to be small.[56]One small randomized study suggested that the NSAID diflunisal had a greater efficacy than acetaminophen.[58]In addition, their findings demonstrate that the various NSAIDs are, on average, equally efficacious.[59]Gastrointestinal, renal, and potential cardiac toxicities must be considered with long-term NSAID use.[56].

During the acute phase following biomechanical injury to the spine, where there are no fractures, subluxation, other serious osseous lesions, or significant neurological sequelae, mild narcotic analgesics may assist patients in minimizing inactivity and safely maximizing the increase in activity, including prescribed therapeutic exercises. NSAIDs and muscle spasmolytics used during the day or at bedtime may also provide some benefit.[18, 50]The best available evidence advocates the use of an antidepressant, analgesic, or both for chronic back pain. When starting a new medication, patients should be educated as to why a medication is chosen and its expected risks and benefits. Patient preferences concerning medications should be considered, especially after they are informed of potential risks. When anxiety lingers regarding the risks or side effects of a medication (eg, NSAIDs or muscle relaxants), a short trial of the medication at a low dosage over 3-4 days can be effective for assessing the patient's tolerance and response to the drug, as well as alleviating patient and physician concerns. Most patients require medications in relatively high therapeutic ranges over a protractile period of time.[60]Patients may be resistant to multiple therapeutic approaches and may require more individualized medication combinations, including other analgesics. Pooled data from large groups of patients have shown that no one medication in any of the various drug classes provides more benefit to the patient than another.[60]Furthermore, predicting which patient will respond best to which medication within that class is impossible. Better studies with greater numbers of patients and longer follow-up times are needed to better compare classes of medications, including simple analgesics, muscle relaxants, and NSAIDs.[54]NSAIDs

NSAIDs contain both analgesic and anti-inflammatory properties and therefore may affect mediators of the pathophysiological process. Clinical trials have demonstrated NSAIDs to be useful as a treatment for pain, but the long-term use of NSAIDs should be discouraged due to the frequent occurrence of adverse renal and gastrointestinal side effects.[18, 52]A 2000 review and analysis of randomized and double-blind controlled trials of NSAIDs as LBP treatment revealed supportive evidence for short-term symptom relief in patients with acute LBP. Evidence of any benefit for chronic LBP or of any specific superiority of one NSAID is lacking.[61, 60]Therefore, the effect of these medications in the management of chronic musculoskeletal pain remains unclear, and no studies have demonstrated a clear superiority over aspirin.[52]Although the research does not support any specific NSAID over others, switching to different chemical families through sequential trials sometimes helps identify an agent that is the most beneficial for an individual patient.[18]Muscle spasmolytics

Muscle spasmolytics or relaxants are traditionally used to treat painful musculoskeletal disorders. As a class, they have demonstrated more CNS side effects than a placebo, sharing sedation and dizziness as common side effects. Therefore, patients should be cautioned about these side effects and weigh them against the potential benefits.[56, 58, 62, 60]A recently published review and analysis of randomized or double-blinded controlled trials showed that muscle relaxants were effective for the management of LBP, but adverse side effects limited their use.[62]With some patients, these medications can only be considered for use at bedtime. Some muscle spasmolytics are also potentially addictive and have abuse potential, especially more traditional agents such as diazepam, butalbital, and phenobarbital.

The category of muscle relaxants includes a heterogeneous group of medications that some experts divide into benzodiazepines and nonbenzodiazepines. Benzodiazepines may be appropriate for concurrent anxiety states, and in those cases, clonazepam should be considered for its clinical use. Clonazepam is a benzodiazepine that operates via GABA-mediated mechanisms through the internuncial neurons of the spinal cord to provide muscle relaxation.[63]Strong evidence shows that another benzodiazepine, tetrazepam, is more effective than a placebo at treating short-term pain and some indicate that it also improves muscle spasms; however, data on long-term outcomes are inadequate.[56]The data on nonbenzodiazepine muscle relaxants are not as strong, but moderate evidence exists for short-term overall improvements, although little or no improvement has been shown in specific pain outcomes.[62]Examples of commonly used nonbenzodiazepine muscle relaxants include cyclobenzaprine, carisoprodol, methocarbamol, chlorzoxazone, and metaxalone. A comprehensive evaluation and meta-analysis of cyclobenzaprines effectiveness showed support for short-term use (< 4 d) with a modest benefit early in LBP treatment, but with the same problematic side effects.[64]Tizanidine is a central -2 adrenoreceptor agonist that was developed for the management of spasticity due to cerebral or spinal cord injury, but also has demonstrated efficacy when compared to other muscle spasmolytics.[65]The muscle spasmolytic effects of tizanidine are thought to relate primarily to centrally acting 2-adrenergic activity at both the spinal cord and supraspinal levels.[66]Several clinical trials have demonstrated the efficacy of tizanidine for the treatment of acute neck and back pain.[67, 68, 69, 70, 71]Controlled studies have demonstrated reduced analgesic use and muscle spasm in patients with acute neck and back pain.[69]Specifically, comparison studies have shown that tizanidine is as effective as diazepam and chlorzoxazone for treatment of these acute conditions.[70]Tizanidine exerts no significant effect on muscle tone, so patients report muscle weakness less often as a side effect than with diazepam or other muscle relaxants.[71]The onset of action of tizanidine is rapid with peak plasma concentrations occurring at 1-2 hours following oral administration.[71]The elimination half-life of tizanidine is approximately 2.5 hours with significant interpatient variability.[71]This rapid onset of action coupled with its muscle spasmolytic and antinociceptive properties has spurred investigation into clinical use not only for the treatment of acute spinal pain with muscle spasm, but also as therapy for other painful chronic muscular conditions.

Neuropathic pain analgesics

Conventional treatments for neuropathic pain, including anticonvulsants, may be appropriate for trial use in specific cases when nervous system structures are symptomatic and for myofascial pain, which may also be a spine-mediated disorder. Neuropathic pain may be seen in association with radiculopathy or myelopathy, and the neurologist may be asked for treatment advice in cases without a clear structural cause, following failed or complex surgical treatment, or when surgical intervention is contraindicated.[18, 72]Antiepileptic drugs (AEDs), such as phenytoin, carbamazepine, and divalproex sodium, have been used by neurologists for years to treat neuropathic pain, including neuralgia and headaches.[18, 72]Only carbamazepine is FDA-approved for trigeminal neuralgia. Recently, several newer AEDs have been scrutinized through research and clinical trials as possible treatments for various neuropathic pain syndromes. These recently developed AEDs have 4 basic mechanisms of action:[54, 73]1. Inhibition of sodium channels

2. Inhibition of calcium channels

3. Regulation of the levels or activity of the inhibitory neurotransmitter GABA

4. Regulation of the levels or activity of the excitatory amino acid glutamate

An anticonvulsant popularly prescribed for chronic pain is gabapentin; however, its exact mechanism of action is unclear. Gabapentin has been demonstrated to be effective in multiple double-blind, randomized, controlled studies for the treatment of neuropathic pain syndromes including postherpetic neuralgia[74, 75], diabetic polyneuropathy[76], and spinal cord injury[77]. It has also been shown to be effective as a treatment for myofascial pain associated with neuropathic pain.[78]Lamotrigine has been shown to be effective in several small studies for the treatment of trigeminal neuralgia[79, 80], peripheral neuropathy[81, 82, 83], and central post-stroke pain[84]. The advantages of this AED include its long half-life, which allows once-daily dosing. On the other hand, a rash, which may develop into toxic epidermal necrolysis, has been reported in up to 10% of patients.[85]Other adverse side effects include headaches, asthenia, dizziness, and oversedation.[85]No studies have addressed whether it will be useful for treating spinal pain syndromes. However, randomized, controlled, double-blind studies to assess its efficacy for neuropathic pain have been strongly recommended.[86]Other contemporary AEDs showing promise as treatments for neuropathic pain in small open-label studies include topiramate[87, 88], zonisamide[89, 90, 91, 92], levetiracetam[93], tiagabine[94], and oxycarbazepine.[95, 96, 97, 98]Double-blind, randomized, placebo-controlled studies in specific neuropathic pain populations with careful monitoring of dosage levels and adverse events are necessary. Application of these medications to cases of refractory spine-related neuropathic pain is empirical, but warrants consideration.

Antidepressants

Tricyclic antidepressants (TCAs) are commonly used in chronic pain treatment to alleviate insomnia, enhance endogenous pain suppression, reduce painful dysesthesia, and eliminate other painful disorders such as headaches. Research supports the use of TCAs to treat both nociceptive and neuropathic pain syndromes.[54, 73, 99, 100]The presumed mechanism of action is related to the TCAs capacity to block serotonergic uptake, which results in a potentiation of noradrenergic synaptic activity in the CNS's brainstem-dorsal horn nociceptive-modulating system.

Also, studies in animals suggest that TCAs may act as local anesthetics by blocking sodium channels where ectopic discharges are generated.[100, 101]Two systematic reviews found that antidepressants reduced pain intensity in cLBP, but no consistent improvement in functional outcomes was measured.[102, 56, 58]Any efficacy for pain relief was seen primarily in tricyclic and tetracyclic antidepressants, whereas selective serotonin reuptake inhibitors (SSRIs) did not show similar properties or efficacy.[102]Little evidence supports the use of SSRIs to attenuate pain intensity, and studies have suggested that these agents are inconsistently effective for neuropathic pain at best.[73]Venlafaxine is a structurally novel antidepressant shown to produce strong uptake inhibition with both serotonin and norepinephrine and have anesthetic properties similar to the TCAs.[103]An uncontrolled case series reported that venlafaxine provided pain relief in a variety of neuropathic pain disorders.[103]Recent studies have shown duloxetine (Cymbalta) to provide significant pain relief compared with placebo for chronic musculoskeletal pain, including low back pain and pain caused by osteoarthritis. In November 2010, the US Food and Drug Administration (FDA) approved duloxetine for treatment of chronic musculoskeletal pain.[272, 273, 274, 275]The usefulness of TCAs is limited, particularly in geriatric populations, due to cardiovascular effects such as tachycardia; anticholinergic side effects including dry mouth, increased intraocular pressure, and constipation; oversedation; and dizziness, including orthostatic hypotension.[104]SSRIs should be considered for a variety of symptoms that commonly accompany chronic pain including reduced coping, depression, anxiety, and fatigue.[104]Overall, SSRIs have fewer adverse side effects than TCAs. Side effects associated with SSRIs include anxiety, nervousness, and insomnia; drowsiness and fatigue; tremor; increased sweating; appetite and gastrointestinal dysfunction; and male sexual dysfunction. Many pain specialists still consider TCAs as first-line pain medications for the treatment of persistent neuropathic pain, especially as an adjunct to peripheral therapies and to manage the adverse influences of chronic illness.

Opioid analgesics

The authors of a 2008 summary and analysis of the best available evidence concluded that all the high-quality studies involving opioid analgesics demonstrated improvements in pain compared with a placebo that were clinically and statistically significant enough to support the their use as a treatment adjunct for patients with cLBP.[105]Although evidence-informed data show stronger support for short- than long-term use, there is still sufficient support for prolonged use as an adjunct treatment for chronic spinal pain.

Randomized controlled trials showed a relatively high dropout rate (20-40%) of patients due to adverse side effects. On average, a third were excellent responders, a third were fair responders, and the remainder tended to be nonresponders. Generally, the evidence for improvements in function is less impressive than reports of a reduction in pain. Opioids appear to be generally safe when used appropriately, and serious side effects are relatively infrequent. Despite contrary opinions among experts, an analysis of the literature also demonstrates that aberrant behaviors in a controlled medical environment, such as recreational abuse and drug divergence, have remained at acceptably low levels.[105]In another evidence-based review, the author cites his findings with more skepticism regarding the long-term use of opioids for chronic back pain.[102, 54, 55]A review of 6 trials compared opioids with placebo or nonopioid analgesics and showed that opioids performed better than the controls in pain reduction; however, in a meta-analysis of the 4 studies that used the best methodology for analysis, this difference was not statistically significant.[106]The conclusions from this systematic review were consistent in demonstrating that opioids are useful for short-term pain relief, but that long-term efficacy or benefit with respect to cLBP is yet to be demonstrated. Furthermore, a review of studies investigating deviant medication-taking behaviors found a wider variation of aberrancy ranging from 5-24%.[106]However, from a practical standpoint, low to moderate doses of opioids may be helpful for activating an injured patient to participate in physical and psychological rehabilitation, including functional restoration, especially with patients whose pain is associated with acute radiculopathy, particularly in those cases that are pre- or postoperative. Opioid analgesics may be helpful for sufferers of chronic intermittent back pain during an acute exacerbation; however, the continuous use of opioid analgesics for chronic neck and back pain is usually reserved as a tertiary treatment option.

Over the past decade, physicians, specifically pain specialists, have adopted a greater willingness to prescribe opioid analgesics for the treatment of refractory spinal pain and radiculopathy. Most patients reclaim what life they can. Inherent dangers include side effects such as respiratory depression cardiac toxicity, bowel dysfunction, sometimes paralysis or obstruction, and hormonal suppression, especially of testosterone, as well as addiction, naive withdrawal, and death from overdosage. The side effect profiles among long-acting opioids are similar, but the cost is variable between current pharmaceutical offerings, which include orally routed methadone, long-acting oxycodone, long-acting morphine, long-acting oxymorphone, and the controlled delivery of fentanyl by transdermal patch.

Several principles apply to prescribing long-acting opioids for chronic pain. These medications should be taken in a time-contingent, rather than pain-contingent manner, and they should only be provided by 1 prescribing physician and pharmacy. The need and purpose of the opioids and their medical necessity should be affirmed by an agreement signed by both patient and doctor and placed in the medical record. The achievement of vocational, recreational, and social goals is a better measure of medication efficacy than subjective estimates of pain relief.[102]For chronic spinal pain, an ongoing, active, preferably independent exercise program aimed at functional restoration should be considered mandatory.

Topical therapy

Topical treatment is drug delivery over or onto the painful site. The medication is delivered through the skin to a shallow depth (< 2 cm) and acts locally, without producing significant systemic serum levels or side effects. A commonly prescribed topical treatment for nociceptive and neuropathic pain is the 5% lidocaine patch. The patch is FDA-approved for the treatment of postherpetic neuralgia and has been demonstrated as an effective treatment for chronic LBP.[107]Almost any imaginable drug combination can be compounded by a competent local pharmacist to create an effective topical application. NSAIDs can be mixed with local anesthetics, AEDs, TCAs, and norepinephrine/epinephrine (sympathetic nervous system) antagonists to calm down pain and autonomic dysfunction associated with chronic spinal-radicular syndromes. Sometimes, compounding topical creams/lotions gives the treating physician the greatest latitude to treat symptoms, especially allodynia, without worrying about the medications' systemic side effects.

Novel/emerging pharmacology

The role of inflammation in causing segmental and radicular pain has been reviewed. Cytokines, released by activated macrophages, mast cells, Schwann cells, and microglia, play a major role in nociception and inducing chronic neuropathic pain.[108]Infliximab is a chimeric monoclonal antibody against TNF-, a cytokine with a known role in eliciting spinal nociception. In a recent study, 10 patients with severe sciatica from disk herniation received intravenous infliximab and were compared with a group who were treated with a periradicular infiltration of saline. The infliximab group showed a more than 75% reduction in pain, and the difference was sustained at 3 months.[109]To date, no published data are available regarding the treatment of mechanical spinal pain or sciatica using etanercept (a TNF- blocker) and anakinra (an IL-1 blocker).

Bisphosphonates, specifically pamidronate, have recently attracted attention as a potential new treatment for mechanical spinal pain involving the diskal and radicular structures. These compounds have demonstrated antinociceptive effects and the capacity to inhibit cytokine release by causing apoptosis of reactive macrophages in experimental animal models.[110, 111, 112, 113, 114, 115, 116]The cytokine IL-2 possesses antinociceptive (analgesic) effects upon the peripheral and central nervous systems. Preliminary animal work has produced an antinociceptive effect in the spinal dorsal horn via IL-2 gene therapy.[117]A new chemical compound, designed to be a NO-releasing derivative of gabapentin, was synthesized and designated as NCX8001. This moiety released physiologically relevant active concentrations of NO consequent to experimentally induced sciatic nerve or spinal cord injuries. Observed results included the inhibition of TNF- and reduced allodynia in the injured rats.[118]Other potential future treatments include drugs targeted at the nociception (opioid) receptor[119, 120]and the NMDA receptor. NMDA receptor antagonists, such as dextromethorphan (DM), ketamine, and memantine, are thought to be beneficial in cases of chronic pain and long-term opioid therapy. DM has been shown to reduce morphine requirements in randomized controlled trials.[121, 122, 123]Ziconotide is a neuronal calcium channel blocker that affects neurotransmitter release from primary nociceptive afferents at a spinal level. Studies suggest that it has promise for patients with chronic refractory neuropathic pain that is unresponsive to opioids.[124, 125]Alternative medications (eg, glucosamine) are widely used by patients, but limited data are available to suggest efficacy. Wilkens et al conducted a randomized, placebo-controlled trial in patients with chronic low back pain (LBP) and degenerative lumbar osteoarthritis (OA) (n=250). Patients received either glucosamine (1500 mg/d PO) or placebo for 6 months. Compared with placebo, glucosamine did not reduce pain-related disability after the 6-month intervention and after 1-year follow-up.[126]Spinal Interventional Procedures

Local anesthetics, corticosteroids, or other substances may be directly injected into painful soft tissues, facet joints, nerve roots, or epidural spaces. They may also be given intrathecally. Therapeutic injections have been advocated to alleviate acute pain or an exacerbation of chronic pain, help patients remain ambulatory outpatients, allow them to participate in a rehabilitation program, decrease their need for analgesics, and avoid surgery. Local injections into paravertebral soft tissues, specifically into myofascial trigger points, are widely advocated. However, a double-blind study to compare local anesthetic with saline injections and a prospective randomized double-blind study to compare dry needling with acupressure spray applications of lidocaine, corticosteroids, and vapor coolants revealed no statistically significant difference in therapeutic effects.

Injections can also be used to irritate pain-sensitive spinal tissues to determine whether they are pain generators. Carefully placed contrast dye or normal saline can provoke a pain pattern similar to the patient's primary complaint. Performed under fluoroscopy, contrast dye will document the targeted structure and provocation site, and it is followed by the application of a local anesthetic to ablate the pain, which further verifies the targets role as a pain generator. Some believe that a successful therapeutic intervention can be achieved by using local anesthetic combined with corticosteroids. Some structures can be denervated by radiofrequency ablation or chemical neurolysis to eliminate pain for a prolonged period of time. These techniques receive some support from evidence-based informed data reviewed in this section.

A comprehensive review of the literature was conducted by Boswell et al in 2007, whereby evidence-based data was published by the American Society of Interventional Pain Physicians (ASIPP). This group of physicians has been extremely open regarding their methodology and more than willing to respond to published criticism by other societies who do not use Spinal Interventional Physicians (SIPs) on their panel of reviewing physicia