Pain of Spinal Origin

Anterior Primary Divisions (Ventral Rami)

To approach the cause of the discomfort experienced by Mr. S., let’s first consider those structures innervated by the lumbar APDs (Box 11-1). The APDs of the lumbar region innervate much of the gluteal and inguinal regions, as well as the entire lower extremity. Although these regions may refer to the low back, they usually are accompanied by more localized pain from the structure that is either injured or affected by some form of pathologic process. More likely causes of back pain originating from structures innervated by APDs (ventral rami) are several muscles, including the psoas major, quadratus lumborum, and lateral intertransversarii. Strain or possibly increased tightness (what some would call “spasm”) of these muscles can be a source of back pain. Abscess within the psoas muscle also is a possible source of pain. The transverse processes (TPs) are innervated by the APD too, and a fracture of a TP or bruise to its periosteum may result in pain (Bogduk, 1983).

Posterior Primary Divisions (Dorsal Rami)

Discomfort such as that experienced by Mr. S. also may arise from structures innervated by the PPDs (dorsal rami) listed in Box 11-2. This list contains some of the most frequent causes of LBP, including the deep back muscles, which receive nociceptive innervation by means of nerves accompanying the vessels that supply these muscles; spinal ligaments (nociceptors are most numerous in the posterior longitudinal ligament, innervated by the recurrent meningeal nerve, and fewest in the interspinous ligament and ligamentum flavum innervated by the PPDs; see Box 11-2 for other ligaments innervated by the PPDs); the zygapophysial joints (Z joints) and superficial and deep fascia. These are all high on the list of possible causes of pain similar to that experienced by Mr. S. (Cavanaugh, 1995). Each of these groups of structures may be affected by a number of pathologic conditions or injuries. The muscles may be strained or affected by areas of myofascial tenderness (“trigger points”) (Bogduk, 1983; Hubbard & Berkoff, 1993). The ligaments may be sprained. Pain from the Z joints may be difficult to localize because each Z joint receives innervation from the PPD of the same level and also from the PPD of the level above (Bogduk, 1976) and below (Jeffries, 1988). The Z joints may be fractured (fracture of an articular process) or inflamed as a result of arthritic changes. Discomfort also can arise from a Z joint articular capsule or synovial fold (Giles, 1987; Schwarzer et al., 1994) that has become entrapped within the Z joint or pinched between the articular surfaces (see Chapter 7). Degeneration of articular cartilage may produce inflammatory agents that may stimulate nociceptors of the Z joint articular capsules. Inactivity of the spinal joints, even if this inactivity is imposed on these joints by muscle guarding, may promote degeneration (Cramer et al., 2004) (Fig. 11-2) and pain (Kirkaldy-Willis, 1988b). In addition, the spinous processes may be fractured or may repeatedly collide with one another (Baastrup’s syndrome). Finally, Sihvonen and colleagues (1995) found that the medial branch of the posterior primary division can become irritated or entrapped along its course, causing weakness of transversospinalis muscles (i.e., semispinalis, multifidus, and rotatores muscles) and low back pain. The LBP in this instance presumably results both from irritation of the medial branch of the posterior primary division and from abnormal stresses and loads being placed on pain generators of the spine as a result of the biomechanical changes caused by the muscle weakness.

Recurrent Meningeal Nerve

Structures innervated by the recurrent meningeal (sinuvertebral) nerve also may be a source of back pain (Raoul et al., 2002). The list in Box 11-3 identifies the structures supplied by these nerves. The periosteum of a vertebral body may be affected by fracture or neoplasm within the vertebral body. The basivertebral veins may be affected by intraosseous hypertension, crush fractures, or neoplasms of the vertebral body (Bogduk, 1983). The epidural veins may be affected by venous engorgement. The posterior aspect of the intervertebral disc (IVD) is also a pain generator (Schwarzer et al., 1994; Cavanaugh, 1995) that can be affected by internal disc disruption, protrusion of the nucleus pulposus through the outer layers of the anulus fibrosus, or tearing (sprain) of the outer layers of the anulus fibrosus (AF). Of related importance is that sensory innervation of degenerated IVDs extends into the deeper layers of the anulus fibrosus. That is, the process of IVD degeneration seems to stimulate the nerves innervating the posterior, lateral, and anterior aspects of the IVD to grow deeper into the IVD, probably making them more capable of providing nociceptive sensation (Yoshizawa, O’Brien, & Thomas-Smith, 1980). Also innervated by the recurrent meningeal nerves is the posterior longitudinal ligament, which can be torn (sprained) during severe hyperflexion injuries or may be pierced by an IVD protrusion. In addition, the anterior aspect of the dura mater may be compressed by an IVD protrusion or irritated by the release of chemical mediators associated with internal disc disruption (see Chapter 7).

Nerves Associated with the Sympathetic Nervous System

Finally, recall that several structures are innervated by nerves that arise directly from the sympathetic trunk and gray communicating rami (Box 11-4). The sensory fibers of these nerves follow the gray rami to the APD, where they enter the spinal nerve. They then reach the spinal cord by coursing through the dorsal roots. Pathologic conditions of the periosteum of the anterior and lateral aspects of the vertebral body, which are innervated by sensory fibers traveling with gray rami, may result in pain. Some of the most common causes of this type of pathologic condition include fracture, neoplasm, and osteomyelitis (Bogduk, 1983). Sprain of the anterior longitudinal ligament or outer layers of the anterior or lateral part of the anulus fibrosis also may result in nociception conducted by fibers that course with the gray communicating rami.

Under certain circumstances, the sympathetic nervous system can play a complex role with regard to pain (Jorgensen & Fossgreen, 1990; Budgell, Hotta, & Sato, 1995; Siddall & Cousins, 1997). Changes in vasculature, changes in perspiration (sudomotor), and changes in nail, hair, and bone structure can accompany chronic pain associated with the sympathetic nervous system (Siddall & Cousins, 1997). This pain often is burning in nature and is associated with increased stimulation of sensory receptors. This is accompanied by an increased perception of pain in areas not associated with tissue damage (hyperalgesia), and also by an increased sensitivity to mechanical stimulation, including mechanical stimulation that previously would not be considered capable of producing pain (allodynia). The mechanism may be related to the finding that nociception from damaged or regrowing nerves and even nearby axons sometimes can be activated by norepinephrine from sympathetic stimulation. This activation is thought to result from alpha-adrenergic (norepinephrine) receptors developing on C (nociceptive) fibers after partial nerve injury (Greenspan, 1997). Once known as reflex sympathetic dystrophy, the term complex regional pain syndrome is now preferred (Plancarte & Calvillo, 1997). The pain of some patients with complex regional pain syndrome is related to the sympathetic nervous system (sympathetically maintained pain), although others’ pain is not (sympathetically independent pain) (Greenspan, 1997). (See Sympathetically Maintained Pain in Appendix II and Complex Regional Pain Syndrome in Chapter 10).

Pain Generators Unique to the Cervical Region

If Mr. S. is also presenting with pain in the cervical region, other structures should be included on the list of possible pain generators. These include irritation of the nerves surrounding the vertebral artery and nociception arising from uncovertebral “joints.”

Nociception arising from almost any structure innervated by the upper four cervical nerves may refer to the head, resulting in head pains and headaches (Campbell & Parsons, 1944; Edmeads, 1978; Bogduk, Lambert, & Duckworth, 1981; Bogduk, 1984; Aprill, Dwyer, & Bogduk, 1990; Dwyer, Aprill, & Bogduk, 1990; Darby & Cramer, 1994; Cramer, 1998). Pain originating from the region of the basiocciput and occipital condyles frequently refers to the orbital and frontal regions (Campbell & Parsons, 1944). A discussion of neck pain and its relationship to headache and head pain has been fully covered elsewhere (Vernon, 2001), and is beyond the scope of this chapter.

Autonomic reactions such as sweating, pallor, nausea, alterations of pulse rate, and other autonomic disturbances frequently have been observed in association with disturbances of the suboccipital and upper cervical spine. The intensity of these autonomic reactions seems to be proportional to the stimulus and proximity of the stimulus to the suboccipital region. The autonomic response ranges from mild subjective discomforts to measurable objective signs (Campbell & Parsons, 1944).

Pain Generators Unique to the Thoracic Region

If Mr. S. should present with discomfort of the thoracic region, the costocorporeal and costotransverse articulations, as well as fracture of the proximal aspect of a rib, should be added to the list of possible pain generators (see Chapter 6). Also a compression fracture of one or more of the thoracic vertebral bodies could be a realistic source of acute pain arising from the thoracic region.

Dorsal Root Ganglia

The neurons located in the dorsal root ganglia (DRGs) serve as modulators of spinal nociception. They contain many neuropeptides (see Chapter 9) associated with the transmission of nociception (e.g., substance P, calcitonin gene–related peptide [CGRP], vasoactive intestinal peptide) (Weinstein, Claverie, & Gibson, 1988). These neuropeptides and other neuromodulators are secreted from the peripheral terminals of sensory nerves that transmit nociception. These substances are manufactured in the cell bodies of the DRG and reach the peripheral terminals (sensory endings) and the synaptic boutons found in the dorsal horn of the spinal cord by axonal transport mechanisms. The presence of neuropeptides and neuromodulators around the receptors may sensitize the receptors, making them more susceptible to depolarization (Weinstein, Claverie, & Gibson, 1988). (See the sections Important Terms and General Concepts Related to Pain, and Modulation of Nociception for more information on the modulation of nociception at the level of the peripheral nerve endings.)

Spinothalamic Tract

The response of the brain to painful stimuli is intricate and complex, and there are several pathways associated with Mr. S.’s LBP. Nociceptive information is conveyed to higher centers by tracts in the anterolateral quadrant of the spinal cord. Two major tracts conduct this information in the cord’s anterolateral quadrant—the spinothalamic tract (also called the neospinothalamic tract) and the spinoreticular tract. The spinothalamic tract conveys nociceptive information, which is perceived as sharp, pinprick-like pain, via fast conducting A-delta fibers. The integrity of this tract commonly is tested during a neurologic examination by asking the patient to differentiate the sensations of sharp versus dull. The cell bodies of the tract neurons are both nociceptive-specific and wide–dynamic-range neurons (sensitive to many types of stimuli) that are located in the dorsal horn primarily in laminae I and V to VII (Basbaum & Jessell, 2000). These axons decussate in the ventral white commissure within one or two segments of entry and ascend in the anterolateral white matter of the cord and through the brain stem. They synapse in the ventral posterior lateral nucleus and posterior nucleus, which comprise the lateral nuclear group of the thalamus (Fig. 11-4, A). From the thalamus, axons of the next order neurons course to the somesthetic region of the cortex, which is the postcentral gyrus and the posterior part of the paracentral lobule of the parietal lobe. As the axons of the spinothalamic tract ascend, body parts are represented in specific regions of the tract. This specific pattern is retained in the cerebral cortex, such that a specific area of cortex corresponds to the region of the body from which the sensory fibers originated. This cortical representation is called the sensory homunculus. The size of the body part represented on the homunculus reflects the amount of sensory innervation devoted to that body area. As mentioned, this unequal neuronal representation may be one reason that localization of sensations, such as pain, is more difficult in one region (e.g., back) than another (e.g., fingertips or lips). The information conveyed in the spinothalamic tract is processed in the region of the sensory homunculus. Here the nociception is perceived as pain that is acute, localized, and discriminatory.

Spinoreticular Tract

The other tract that ascends in the anterolateral quadrant is the spinoreticular tract (Fig. 11-4, B and C). The cell bodies of the spinoreticular tract are located in laminae VII and VIII. The nociceptive input to these neurons is polysynaptic; therefore these neurons are likely involved with more complex response properties of pain. The axons of these neurons ascend to the reticular formation of the brain stem and to the thalamus. The reticular formation is a complex network of neurons located throughout the core of the brain stem. It has numerous functions and is a major component of the ascending reticular activating system (ARAS), along with the thalamus and cerebral cortex. The ARAS provides the circuitry through which arousal and attentiveness are maintained. The tract neurons synapsing in the reticular formation form complex connections within this region and subsequently project to brain stem nuclei, the hypothalamus, and the midline and intralaminar nuclei of the thalamus. These latter nuclei are part of the medial nuclear group of the thalamus. Subsequent thalamic projections course to widespread, nonspecific areas of the cerebral cortex. In addition, the paleospinothalamic tract (also known as the spinoreticulothalamic tract) contributes collateral branches to the reticular formation as it ascends through the brain stem to the midline and intralaminar thalamic nuclei. The spinoreticular tract and spinoreticulothalamic fibers are not somatotopically organized. The nociceptive information conveyed in these fibers also may be involved with the generation of chronic pain and the qualities associated with that sensation. The focusing of the individual’s attention on the painful area is most likely a function of the ARAS.

Dimensions of Pain

Pain appears to be of two dimensions. One is a sensory portion that is involved with identifying the location, intensity, quality, and other characteristics of the pain for an appropriate motor response. The other is the dimension of affect and motivation. This is the subjective awareness of the unpleasantness of the pain: the desire (motivation) to terminate, reduce, or escape the stimulus. It includes the emotions involved with present, short-term, or long-term implications of the pain (i.e., interference with one’s life) and the cognitive processes of how to cope with the pain. Pain is a complex sensation, and multiple pathways that ascend both in series and in parallel terminate in numerous brain stem and cortical regions to participate in its processing. The pathway that serves the dimension of pain sensation is the (neo)spinothalamic pathway, sometimes called the lateral and more direct pathway. As discussed, this pathway projects to the somatosensory cortex, which in turn projects to other cortical areas such as the posterior parietal lobe and insular cortex. From these two areas, projections continue to other areas (e.g., the amygdala and anterior cingulate cortex) that have reciprocal connections with the prefrontal cortex. This pathway may be involved not only with the discrimination of the rudimentary aspects of pain such as intensity, quality, and location, but also with the integration of numerous somatosensory inputs. The integration of these inputs provides an overall feeling of the seriousness or threat of the pain stimulus to the body and self (Price, 2000). The aspect of affect and motivation to pain sensation is served by numerous pathways sometimes collectively called the medial pathway (Cross, 1994; Hudson, 2000; Sewards & Sewards, 2002). The spinoreticular and spinoreticulothalamic tracts (see previous section) and spinomesencephalic and spinohypothalamic tracts (see Chapter 9) terminate in brain stem nuclei, the thalamus, and hypothalamus (Price, 2000). Processing at these levels may produce elementary aspects of pain behavior by involving autonomic activation, escape responses, arousal, and fear. These attributes occur early in pain-processing stages when fear, defensive behavior, and visceral responses occur. The thalamic nuclei of this pathway (midline and intralaminar) project to the limbic system, which allows an individual to perceive a sensation as being uncomfortable, aching, or hurting (Song & Rupert, 2005). The component of the limbic system receiving this input is the anterior cingulate cortex (see Fig. 9-14). This region is considered to be a major cortical area for processing the emotional (motivational) component of pain (Hudson, 2000; Price, 2000; Raineville, 2002; Sewards & Sewards, 2002). The anterior cingulate cortex is indirectly and directly connected with many other areas including the posterior cingulate cortex, amygdala (which functions in the memory aspects of painful experiences), insular cortex (which functions in the autonomic component of the entire painful episode), parietal cortex, and prefrontal cortex. Because of these interactions, the anterior cingulate cortex may be a region that integrates pain information received from sensory cortices concerning recognition and threat of the painful experience with information received from the prefrontal cortex. This integration is considered important for individuals like Mr. S. to plan how to respond and cope with the painful experience.

General Concepts Related to Pain

Modulation at the Level of the Peripheral Nerves and Spinal Tissues (Pain Generators)

Damage to or section of a peripheral nerve results in biochemical and neurophysiologic changes in the nerve and surrounding tissues that lower the threshold of the affected nerve and the nerve endings of other nerves within the affected surrounding tissues (Fig. 11-5, A through C). These changes are mediated by the nerve endings themselves or by the DRG, and also can cause the nociceptive fibers to fire spontaneously (ectopically). In addition, a decrease in the blood supply anywhere along the course of myelinated nerves can cause a reduction of the myelination that also can lead to ectopic firing of the nerves. Ectopic firing of the afferent fibers is interpreted by the CNS as if a real stimulus onto a specific receptor had produced the event, and these impulses can be perceived as stabbing (sharp), radiating, or burning pain (Siddall & Cousins, 1997). Of related importance is that a much higher incidence of blocked lumbar segmental arteries and the middle sacral artery exists in patients with LBP compared with age-matched controls (Kauppila & Tallroth, 1993). Recall that these arteries supply the dorsal and ventral roots, spinal nerve, proximal portion of the anterior primary division, and a considerable portion of the posterior primary division and its medial and lateral branches. Therefore ischemia to any of these nerve fibers (with the exception of the ventral roots) can lead to an increase in the amount of perceived pain through ectopic firing, even though no true peripheral nociceptive stimulus may be present.

Nerve fibers in the region become more sensitive to stimulation once tissue damage occurs, and motions or pressures that normally would not cause pain may then be perceived as quite painful (allodynia). The phenomenon of increased sensitivity of nociceptors after tissue damage is known as peripheral sensitization or primary hyperalgesia. Primary hyperalgesia (sensitization) has been verified experimentally in spinal tissues (Yamashita et al., 1990). This type of sensitization is caused by a combination of pain-mediating chemicals (e.g., substance P, bradykinin, histamine) released from tissue cells in the area of tissue damage, including inflammatory tissue cells (e.g., lymphocytes, mast cells), as well as neurotransmitters and related substances released from the nerve endings innervating the injured tissues. These events can lead to a prolonged sensation of pain to nociceptive stimuli. In addition, certain nociceptors, sometimes called “silent nociceptors,” which normally have an extremely high threshold and do not fire even with mild to moderate tissue damage, begin to fire frequently once this “chemical soup” of pain mediators is found in the damaged tissues. Silent nociceptors have been well documented in muscle tissue and joint capsules and are thought to be present in the IVD. They are not found in skin (Cavanaugh, 1995; Greenspan, 1997). These silent nociceptors are also a component of peripheral sensitization. Conversely, endogenous opioids in the peripheral tissue may be released and activate opioid receptors found on the afferent fibers, thus modulating the membrane potential of the afferent fibers and resulting in a decrease of nociceptive input and ultimately in pain perception (Siddall & Cousins, 1997). Therefore the response of the peripheral nervous system to tissue damage is a complex one, and is the result of the competitive effects of pain mediators and endogenous opioids in the region surrounding the sensory nerve endings or a damaged nerve.

Modulation in the Spinal Cord

The neurotransmission of nociception can be modulated at the segmental level by the action of interneurons in the dorsal horn (Fig. 11-6). This mechanism has been known to exist since Melzack and Wall (1965) proposed the gate control theory. Since then the dorsal horn, and especially the superficial dorsal horn, has been extensively investigated. The data from this research have led to numerous questions concerning the details of the gate control theory, and subsequently the theory was revised. However, the general concept of the gate control theory appears to be accepted (McMahon, 1990; Willis & Coggeshall, 1991). Briefly this theory states that increased activity of large-diameter, low-threshold (non-nociceptive) afferents competitively inhibits the transmission of small-diameter (nociceptive) afferent fibers, thus decreasing nociceptive input by tract neurons to higher centers, resulting in a decrease in the perception of pain. This concept has led to effective therapies for relief of pain, such as transcutaneous nerve stimulation and dorsal column stimulation (McMahon, 1990).

The inhibition of the tract neurons conducting nociception most likely comes from a population of interneurons located in lamina II (substantia gelatinosa). Many of these interneurons use enkephalins as neurotransmitters. These interneurons receive excitatory input (possibly indirectly) from large-diameter, low-threshold mechanoreceptive afferents. The interneurons, in turn, inhibit the neurons conducting nociception (Basbaum, 1984). Consequently, a balance between the non-nociceptive inhibitory input and the excitatory nociceptive input from small-diameter fibers is mediated by inhibitory interneurons, and is likely to be necessary for the normal processing of nociception (McMahon, 1990). This balance is probably the result of modulation originating from both the complex circuitry of the superficial dorsal horn and the descending supraspinal pathways, and may explain, in part, the wide variability associated with tolerance to pain. In addition, stimulation of the non-nociceptive mechanoreceptors immediately after the activation of C fiber nociceptive afferents can reduce the output of the nociceptive neurons and possibly reduce the amount of central sensitization associated with activation of pain pathways. Further research is necessary to clarify this circuitry and its relationship to the descending input from regions in the brain stem (see following discussion).

Supraspinal Modulation

Evidence from studies in which electrical stimulation of regions of the brain stem produced analgesia (Basbaum & Fields, 1978) indicates that descending pathways can modulate nociceptive signals. One of the components of this endogenous pain control system is the periaqueductal gray (PAG) matter of the midbrain. This region has a major projection to the nucleus raphe magnus, which is located in the midline of the rostroventral medulla (see Fig. 11-6). This nucleus is rich in the neurotransmitter serotonin. Serotonergic fibers course into the dorsolateral funiculus of the spinal cord (raphe-spinal tract) from this region, and many fibers synapse on neurons in the superficial dorsal horn (laminae I and II). A second pathway stimulated by the PAG originates in the lateral tegmental nucleus of the brain stem and sends adrenergic neurons to stimulate interneurons that use enkephalin as a neurotransmitter. These interneurons also are found in the superficial dorsal horn of the spinal cord (Basbaum & Fields, 1984; Hendry, Hsiao, & Bushnell, 1999). The superficial dorsal horn receives input from afferent fibers conveying nociception. In addition, this is the location of the origin of the spinothalamic tracts (Basbaum & Fields, 1978; Jessell & Kelly, 1991) and the area involved with the segmental modulation of nociception (see previous section). The descending fibers synapse on several types of neurons. These include the inhibitory interneurons containing enkephalins (an opioid peptide) just discussed, and also the nociceptive projection (tract) neurons. The opioid-containing (enkephalin) inhibitory interneurons are close to both primary nociceptive afferents and the tract neurons. In fact, both the axonal afferent nociceptive endings and the dendrites of the tract neurons contain opioid receptors (Jessell & Kelly, 1991). Pharmacologic studies have shown that the release of opioid peptides from the inhibitory interneurons blocks transmission of nociception by two mechanisms (see Fig. 11-6). One proposed mechanism is by binding to receptors on the presynaptic terminals of the primary afferent fibers and inhibiting their release of neurotransmitters, such as substance P. The enkephalins may bind to µ-opioid receptors by diffusing from their site of release to the presynaptic membrane of the primary afferent fibers (Basbaum, 1987; Besson, 1988; Jessell & Kelly, 1991; Basbaum & Jessell, 2000). The effect of these enkephalins on the presynaptic membrane is to hyperpolarize the membrane or shorten the duration of the incoming action potential (or both), which leads to a decrease in the amount of neurotransmitter released, and therefore a reduction of nociceptive information being transmitted to the CNS.

The second mechanism by which inhibitory interneurons can mediate spinal neurotransmission of nociception is by directly synapsing with the postsynaptic membrane of the tract neuron (see Fig. 11-6). This occurrence has been well documented (Basbaum, 1987; Besson, 1988; Jessell & Kelly, 1991). Through these connections, the tract neuron is made less excitable (by increasing K⁺ conductance and thus hyperpolarizing the cell) and nociceptive transmission can be reduced substantially. Recall that the descending fibers from the PAG stimulated the enkephalin interneurons. Therefore analgesia can be produced by neural stimulation of the PAG. Analgesia also can be produced by the administration of opiates, such as morphine, into the CNS. The areas activated by the opiates are similar to those that produce analgesia when the PAG, rostroventral medulla, and enkephalin interneurons in the superficial dorsal horn are stimulated by normal neural transmission. This lends credence to the theory that endogenous opioid peptides, which have been found in the brain, can activate the descending control system to modulate pain perception (Jessell & Kelly, 1991).

In addition to the serotonergic descending pathway, other fibers descend from the pons (Basbaum, 1987; Hoffert, 1989) and appear to be involved with modulation of the nociceptive system. These descending fibers contain norepinephrine and also appear to inhibit nociception at the dorsal horn level. However, at the same time, collateral branches of these fibers synapse on the serotonergic neurons of the raphe nuclei. The subsequent release of norepinephrine at this level results in tonic inhibition of the raphe-spinal neurons (Basbaum, 1987), which tends to increase nociceptive transmission in the dorsal horn. Thus both systems provide a descending component to the mechanism for controlling pain. Feeding into these two systems is the nociceptive information transmitted through the ascending pathways (Basbaum & Fields, 1978). These ascending pathways possibly include the spinomesencephalic tract and input from the reticular formation (see Chapter 9). Also, possibly feeding into the two descending systems is stress-induced input channeled through the limbic system and hypothalamus (Jessell & Kelly, 1991). Therefore supraspinal modulation of pain is a complicated process that can be modulated at many levels by numerous different ascending and descending systems. This allows significant variability in the overall perception of pain based on the degree of tissue injury, physical activity of the individual, stimulation of other sensory systems, mental activity, psychological factors (including stress), and other influences. Consequently, once the physical cause of Mr. S.’s problem is determined, many factors must be considered when developing a comprehensive treatment plan.

After a brief pause to review the nature of mechanical back pain, the clinician enters the room to greet Mr. S., and is now mentally prepared to consider the pain that is bothering Mr. S.

Roles of the Dorsal Root Ganglia and Nerve Roots in Pain of Radicular Origin

The results of compression on the DRGs and nerve roots are myriad. Notice in Box 11-9 that mechanical deformation affects not only the nerve fibers within the dorsal root, but also the blood vessels and connective tissue elements associated with the root (Dahlin et al., 1992). The spinal cord, nerve roots, and especially the dorsal root ganglia are more susceptible to compression than peripheral nerves, and compression or inflammation anywhere along the cauda equina or DRGs can be associated with radiculopathy (Garfin et al., 1995). The distal side of the DRG is particularly sensitive to compression (Parke, 2005). Weinstein (1988) has stated, “The intensity of the pain and its radicular nature are dependent on the strength of the stimulus” (i.e., amount of compression). As noted, the DRG is particularly sensitive to compression (Hanai, Matsui, & Hongo, 1996). Notice also in Box 11-9 that pressure on the DRG results in DRG edema. This edema is primarily from venous congestion, which can occur with little pressure on the DRG (Parke, 2005). The edema eventually results in decreased blood flow to sensory nerve cell bodies because oxygenated blood from the externally located DRG capillaries can no longer easily reach the neuronal cell bodies. Lack of oxygenated blood to the DRG results in neural ischemia, and the neural ischemia is perceived as radicular pain (Rydevik, Myers, & Powell, 1989). Short-term neural ischemia has also been related to a decrease in the speed impulses are transmitted along nerves (i.e., decreased nerve conduction velocity); studies of the relationship between long-term neural ischemia and nerve conduction velocities are still needed (Takamori et al., 2011). Compression of nerve roots has also been found to decrease axoplasmic flow within the neurons, affecting neuron (including neurotransmitter) metabolism; these changes may be another reason for decreased nerve function following nerve root compression (Kobayashi et al., 2005a). In addition, histamine-like chemicals and membrane-bound substances (e.g., phospholipase A₂) within the nucleus pulposus (not in the anulus fibrosus) of a prolapsed or extruded IVD cause inflammation of the DRG, which can result in radicular pain, demyelination of nerve roots, and decreased nerve conduction velocities in the nerves affected by these chemical mediators (Rydevik, Brown, & Lundborg, 1984; Garfin, Rydevik, & Brown, 1991; Chen et al., 1997; Otani et al., 1997; Kayama et al., 1998; Özaktay, Kallakuri, & Cavanaugh, 1998). In addition, nucleus pulposus in contact with nerve roots has been found to result in increased endoneurial fluid pressure, causing what has been called a “compartment syndrome of DRG.” This compartment syndrome decreases blood flow in the DRG and increases venous congestion, augmenting radicular pain (Yabuki et al., 1998; Yabuki, Igarashi, & Kikuchi, 2000; Parke, 2005). Ectopic impulses (depolarization of neurons without extrinsic stimulation) are thought to occur from these changes and as a result to be one cause of radicular pain. These impulses normally occur during slight mechanical pressure on the DRG, and may continue for up to 25 minutes after the removal of the compression. These continued ectopic impulses are known as “after-discharges.” Such ectopic discharges may be related to the demyelination and inflammation, augmented by persisting changes in blood flow (e.g., venous congestion) mentioned earlier in this paragraph (Parke, 2005). In addition, substance P (a neuromodulator) has been found in the DRGs of experimentally chronically compressed sensory roots in pigs (Cornefjord et al., 1995), and voltage-dependent ion channels are altered in DRGs associated with radiculopathy (Abe et al., 2002). These findings also may contribute to the ectopic discharges. Finally, the receptive fields of the neurons supplied by a compressed DRG are sensitized and expanded after the compression is removed (Cavanaugh, 1995; Hanai, Matsui, & Hongo, 1996). If compression of a dorsal root occurs at two sites (e.g., in the lateral recess and in the intervertebral foramen proper) or rapidly, the events described in this section may be significantly augmented (Parke, 2005).

Exposure of the DRG and nerve roots to both normal and degenerated nucleus pulposus (without compression of the roots) also causes a decrease in the nerve conduction velocities of the axons passing through them (Otani et al., 1997; Iwabuchi et al., 2001; Ozawa, Atsuta, & Kato, 2001) that can take up to 8 weeks to resolve after exposure to nucleus pulposus tissue (Otani et al., 1997). Added to this are the findings that nucleus pulposus placed on nerve roots results in the induction of hyperalgesia and mechanical allodynia in rats (Anzai et al., 2002; Park et al., 2011). In experiments using rats, Anzai and colleagues (2002) found that nucleus pulposus placed on nerve roots caused wide–dynamic-range neurons of the dorsal horn of the spinal cord to have “enhanced responses to noxious stimuli for hours.” One potential mechanism appears to be related to the expression of the cytokine fractalkine in the spinal cord, which affects both neurons and glia (Park et al., 2011).

The dorsal and ventral roots receive sensory innervation themselves via nervi nervorum. The nervi nervorum provide another mechanism by which pressure on the nerve roots can result in pain. The nervi nervorum are most sensitive to stretch, which may help to explain the effectiveness of orthopedic tests designed to stretch the spinal nerve and nerve roots (e.g., the straight leg raise test) (Cavanaugh, 1995). The dorsal and ventral roots (ventral roots only through stimulation of nervi nervorum) originally were verified as a source of back pain by Smyth and Wright (1958), who tied nylon ligatures around nerve roots of patients during lumbar disc surgery and then pulled on the ligatures during the postsurgical recovery period. They found that nerve roots associated with IVD prolapse were much more sensitive to pulling (stretching) of the ligatures than adjacent nerve roots.

The nerve roots in the IVF may respond to pressure differently than those comprising the cauda equina within the spinal canal. The cauda equina may be more sensitive to compression than the distal aspects of the dorsal roots (Dahlin et al., 1992), and even a small amount of pressure (compression) may produce venous congestion of the intraneural microcirculation of nerve roots in the cauda equina (Olmarker et al., 1989). As mentioned when discussing DRGs, the presence of nucleus pulposus (NP) cells (not extracellular matrix) on porcine cauda equina also results in decreased nerve conduction velocities. The decreased conduction velocities result from Schwann cell damage (Olmarker, Rydevik, & Nordborg, 1993; Olmarker et al., 1996, 1997). Kirkaldy-Willis (1988b) stated:

Other sensory and even motor modalities are also influenced when a dorsal nerve root is affected (Box 11-11). Therefore radicular pain usually is accompanied by paresthesia, hypesthesia, and diminished reflexes (because the sensory limb of the deep tendon reflex is affected). For the reason that the dorsal root and ventral nerve root are adjacent to each other, compression of the dorsal root usually is accompanied by compression of the ventral nerve root as well. In addition to stimulation of the nervi nervorum of the root, which results in pain, compression of the ventral (motor) root results in motor weakness. Therefore radicular pain often may be accompanied by motor weakness (see Box 11-11). Because of the decreased motor function found with compression of the ventral roots, needle electromyography of the paraspinal muscles (innervated by the dorsal rami, or posterior primary divisions, to be distinguished from the dorsal roots) can be useful in verifying the diagnosis of radiculopathy in difficult cases (Haig, LeBreck, & Powley, 1995).

Chronic compression of nerve roots and DRGs results in other unique physiologic responses. For example, serotonin, a neurotransmitter previously discussed as being involved in pain modulation, may be released by aggregating platelets and result in vasoconstriction in the blood vessels supplying nerve roots that are chronically compressed but causes vasodilation of vessels of healthy (uncompressed) nerve roots (Sekiguchi et al., 2002). However, the chronically compressed nerve roots also seem to adapt to some extent. Kikuchi and colleagues (1996) found that chronically compressed nerve roots are less sensitive to acute compression than noncompressed nerve roots.

What may seem to some as an unrelated activity can cause changes in the DRG in certain individuals. Whole body vibration has been established as one cause of LBP and has been linked to IVD protrusion (especially when combined with repetitive, sudden, intense [“shock”] loading of the IVD) (Yates & McGill, 2011). In addition, morphologic changes in the DRGs (i.e., increase in number of mitochondria, lysosomes, and nuclear membrane clefts) have been found with whole body vibration in rabbits. These changes are consistent with the formation of neuropeptides. This suggests the potential for similar changes in humans with occupations attended by whole body vibration. Such occupations include truck driving, certain highway maintenance, and some construction occupations (McLain & Weinstein, 1991). Because Mr. S. has this type of occupation (driving a truck), his sensory neurons may be sensitized to additional stimulation.

Combined Somatic Referred and Radicular Pain

In addition to the radicular signs and symptoms just discussed, Mr. S. also has diffuse LBP. This leads the clinician to suspect that he may be experiencing two different types of pain: somatic referred (nociceptive) and radicular (neuropathic) pain.

Recall that pain of somatic origin displays certain characteristics. Some of the generalized discomfort experienced by Mr. S. may be emanating from a lesion of a somatic structure. A review of possible somatic pain generators is useful, because only those structures innervated by nociceptive nerve endings are capable of producing pain (see Boxes 11-1 through 11-4).

Mr. S. also appears to be experiencing pain and some loss of function resulting from irritation of the left S1 nerve roots (dorsal and ventral). Therefore Mr. S. is simultaneously experiencing both radicular pain and pain arising from somatic structures. This is not unusual. Pain of spinal origin frequently arises from more than one pain generator. In addition, the referral zones of somatic referred pain and radicular pain frequently overlap. A patient with the symptoms and signs described for Mr. S. could be experiencing somatic referred pain originating from the posterior aspect of the anulus fibrosus, posterior longitudinal ligament, and anterior aspect of the dural root sleeve. The nociceptive input from these structures is carried by the recurrent meningeal nerve to the dorsal horn of the spinal cord and then follows the described pathways to higher centers.

The radicular pain and functional deficits (i.e., decreased Achilles reflex and loss of plantar flexion) of the left lower extremity described in this particular case are caused by compression of the S1 nerve roots between the protruding L5 IVD and the left superior articular process of S1. The mechanisms of nociception arising from compression of the dorsal root, as well as the mechanism of the loss of motor function from compression of the ventral root, were described earlier in this section.

Unique Role of the Intervertebral Discs in Low Back Pain

Like Mr. S., many patients experience low back and leg pain resulting from pathology of the IVD and from pressure on nerve roots or a DRG from a protruding IVD. A great deal of research related to the biology of the IVD and its role in back pain has been completed in recent years. This section summarizes some of the key findings of that research.

Interaction between the Zygapophysial Joints and Intervertebral Discs

Even though the Z joints probably are not the primary source of back pain in the case of Mr. S., the structures of the posterior vertebral arch, and particularly the Z joints, are related to 15% to 63% of spine-related pain, depending on the region of the spine (Manchukonda et al., 2007). The Z joints also may contribute to radicular pain of discal origin, because Z joint facet arthrosis may further decrease the space available for the exiting nerve roots (Kirkaldy-Willis, 1988a) (Fig. 11-12). In addition, the inflammatory cytokines associated with Z joint inflammation (Igarashi et al., 2004) could quite conceivably affect the exiting nerve roots in the same way cytokines from PNP can cause radicular pain; however, more research is needed to confirm the effects of Z joint inflammation on the exiting nerve roots and spinal nerve. Chapter 7 discusses the role that may be played by facet arthrosis in the development of spinal (vertebral) canal stenosis and of IVF stenosis.

The reverse also is true. Disc degeneration can alter Z joint motion both at the level of degeneration and at adjacent levels (Li et al., 2011). This altered motion along with the narrowing of the IVD may lead to increased stress on the Z joints. This can result in somatic pain, not originating from the articular cartilage but from pressure on the subchondral bone underlying the articular cartilage. The added pressure on the Z joints secondary to disc degeneration also may result in a small piece of soft tissue (articular capsule or Z joint synovial fold) being pinched between the facets (Hutton, 1990), which can also cause pain.

Recall that lumbar radiculopathy may be caused by chemical irritation. This also has been reproduced by selective nerve sheath injection with hypertonic saline (Rauschning, 1987). In addition, escape of radiopaque contrast medium into the nerve root canals (IVFs) has been repeatedly observed during facet joint arthrography. Because extraarticular synovial fluid is known to have strong tissue-irritating properties, Rauschning (1987) believes that “leakage of synovial fluid from ruptured intraspinal synovial cysts or weakened facet joint capsules may cause pain and possibly transient nerve root dysfunction.” Therefore simultaneous radicular pain and somatic pain arising from the Z joints are a real possibility (see Fig. 11-12).

Other Considerations

The work of Bogduk (2005) provides a clear, well-organized, and well-referenced account of structures of the spine receiving nociceptive innervation. It also describes the mechanisms, as well as they are understood, of somatic referred and radicular pain. The books of Kirkaldy-Willis (1988a,b) and Haldeman (2005) and the papers by Cavanaugh (1995), Greenspan (1995), and Siddall and Cousins (1997) provide excellent correlations between the basic science considerations of pain of spinal origin and clinical practice.

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