CHAPTER 171 Dorsal Root Entry Zone Lesions
Management of chronic pain has graduated over the past few decades to a multidisciplinary approach, and neurosurgical methods, the mainstay of the neurosurgeon’s armamentarium, have evolved from mostly ablative to mostly neuromodulatory. Neuroaugmentative procedures such as spinal cord stimulation have gained increasing acceptance in recent years, largely because of their minimal invasiveness. Additionally, the substantial and prolonged pain relief obtained with these procedures, their cost-effectiveness, the ability to repeatedly reprogram implant technology, and the rarity of complications have all influenced the adoption of neuromodulation as the current surgical pain treatment of choice. Ablative procedures, in particular, percutaneous approaches, nevertheless remain a standard form of treatment of certain conditions such as trigeminal neuralgia. More traditional destructive procedures, such as anterolateral cordotomy, remain an option for patients with certain cancer-related pain such as Pancoast’s syndrome or breakthrough pain resistant to pharmacotherapy. Dorsal root entry zone (DREZ) lesions, although not as frequently performed as a few decades ago, remain a potent form of therapy for management of pain from brachial plexus avulsion and other spinal cord injuries (SCIs) and several types of cancer pain.1,2 Nucleus caudalis DREZ has been shown to be effective in the treatment of anesthesia dolorosa, atypical facial pain, postherpetic pain, and some deafferentation pain.3
Pain Mechanism
Pain-signaling impulses originating in peripheral nociceptors are transmitted by first-order neurons, which have their cell bodies in the dorsal root ganglion. These fibers are either small myelinated (Aδ) or unmyelinated (C) axons that carry impulses from polymodal nociceptors or nociceptive-specific terminals, respectively.4 Second-order neurons, with cell bodies in the dorsal horn of the spinal cord, cross the midline and ascend in the contralateral spinothalamic tract to relay in the thalamus, from where third-order neurons project to the postcentral gyrus (via the internal capsule).
The “H”-shaped configuration of the gray matter of the spinal cord was first described by Rolando in 1824.5 Subsequently, Rexed described discrete laminae in the central gray matter of the spinal cord. The significance of this arrangement in the dorsal horn is that unmyelinated C fibers synapse in laminae I and II whereas the small myelinated Aδ fibers synapse in laminae I, II, and V. C fibers project to the spinoreticulodiencephalic tract (also known as the paleospinothalamic tract), whereas Aδ fibers project to the anterolateral white funiculus (also known as the neospinothalamic tract).4,6–9
Abnormal electrical activity has been documented in the dorsal horn in experimental animal models of brachial plexus avulsion and other SCIs. The concept of DREZ lesions involves surgical destruction of these second-order neurons of the ascending nociceptive pathway. Destruction of the DREZ and superficial dorsal horn is thought to abolish this abnormal electrical activity and thus help relieve pain.10,11
Historical Perspectives
Attempts at DREZ lesions were first made in 1972 in Lyon, France, by Sindou.2,12 He successfully used a technique of microcoagulation of the dorsal rootlets in a patient with Pancoast’s syndrome and termed the procedure selective posterior rhizotomy. Further attempts at the procedure were made by Nashold and colleagues in 1974 with radiofrequency (RF) thermocoagulation.2,13 They coined the term DREZ operation and championed the merits of the procedure. Later, success was reported with lasers by Levy and coworkers, Powers and associates, and Stranjalis and Torrens14–18 and with ultrasonic techniques for DREZ lesions by Dreval and Kandel and associates.19,20 In recent years, Spaic and coauthors have advocated a microsurgical technique of incising the dorsolateral sulcus and suctioning the dorsal horn, but it would appear that pain control rates with this technique are not statistically different (P < .5) from the standard procedure.21
Anatomic and Physiologic Considerations
In his classic paper, Sindou noted that in the dorsal horn of the spinal cord, afferent fibers are segregated spatially according to their size and destination.2,12 About 1 mm outside the spinal cord, the large and small fibers in the dorsal roots, which are arranged somewhat randomly in the afferent nerve fibers, undergo reorientation. Each dorsal root divides into 4 to 10 rootlets, each 0.25 to 1.5 mm in diameter and varying according to level.2,12 The small myelinated and unmyelinated fibers carrying nociceptive impulses course to the lateral side, which makes them appropriately situated to enter into the tract of Lissauer, where they run for one or two segments before penetrating the gray matter of the spinal cord.4,22,23 Because the nociceptive fibers preferentially terminate in lamina I and the substantia gelatinosa (laminae II and III), they are amenable, by virtue of their superficial position in the spinal cord, to surgical lesions without substantial risk of damage to other ascending or descending pathways.7,23–25 In a human cadaveric study of DREZ lesions in the cervicothoracic region, it was found that the average number of rootlets of the C5 to T1 roots was approximately 7.76 + 3.2, with C6 having the most rootlets. The average angle of the inferior rootlets with the longitudinal axis of the spinal cord at each root level from C5 to T1 decreased gradually from 65.6 ± 3.68 to 19.8 ± 2.98 degrees. On cross-sectional studies it was noted that the average length of the dorsal horn was 3.47 ± 0.31 mm (range, 3.10 to 3.75 mm) and the average width was 1.35 ± 0.07 mm (1.20 to 1.45 mm). The angle between the longitudinal axis of the dorsal horn and the sagittal plane of the spinal cord decreased gradually from 29 to 43 degrees, with an average of 35.9 ± 1.28 degrees.26
The dorsal horn essentially consists of central projections of primary neurons, intrinsic dorsal horn neurons, and ascending and descending tracts. It is theorized that the final mechanism underlying pain after SCI is deafferentation, which leads to permanent anatomic and neurochemical changes in the intrinsic dorsal horn neurons and thereby results in chronic pain. It is also possible that the modulating effect of the descending inhibitory impulses on the dorsal horn neurons is modified or lost in such cases.23,27,28 Woolf proposed a classification of the different physiologic states (modes) of the dorsal horn: mode 1—control state; mode 2—suppressed state (as in neurostimulation); mode 3—sensitized state; and mode 4—reorganized state.29 Mode 4 represents a potentially irreversible reorganization of the circuitry of the dorsal horn region. A shift from mode 1 to mode 4 occurs when the highly structured organization of the dorsal horn is modified by degenerative or traumatic changes, which leads to alteration of sensory processing in the dorsal horn. Loss of afferent input to the dorsal horn neurons may also result in upregulation of postsynaptic receptors (denervation hypersensitivity) and adversely affect segmental modulatory (inhibitory) mechanisms, thereby dramatically altering processing of input in the dorsal horn.4,22,23,27 Regeneration may also occur at these sites, and it has been documented that the large myelinated fibers that normally terminate in the deeper laminae may grow into lamina II (the site of C-fiber terminals).4,23 The formation of new synapses would therefore affect the way that the central nervous system processes low-threshold mechanical impulses and lead to their perception as pain. DREZ lesions may interrupt the mechanism of such pain by ablation of the dorsal horn structures involved in generating nociceptive impulses as a result of deafferentation. When Falci and colleagues performed electrophysiologic studies on the DREZ for intraoperative guidance in patients with SCI, they documented spontaneous electrical hyperactivity (higher voltage and frequencies) in the region.10 Using this as a guide to localization of the DREZ, they were able to achieve 100% pain relief in 88% of their patients.
Indications
Since introduction of the technique, DREZ lesions have been applied to treat a wide range of pain conditions, most of which are a form of central or deafferentation pain caused by different conditions ranging from brachial plexus avulsion, SCI, phantom limb, and other complex regional syndromes. DREZ lesions have also been applied to treat pain conditions caused by herpes zoster, cancer, and even spasticity.11,30–32
Despite a plethora of study data, specific application of DREZ lesions and safety guidelines are lacking.33
Brachial Plexus Injury Pain
Avulsion of the dorsal root and the resultant gliosis lead to scar formation in the dorsal horn and substantia gelatinosa. Such scar formation may give rise to loss of the inhibitory effects of large-caliber sensory fibers and to spontaneous activity in nociceptive-specific and wide–dynamic range (polymodal) neurons, which may be responsible for perception of pain after brachial plexus lesions.34,35
Brachial plexus injuries are frequently associated with avulsion of the dorsal or ventral root, or both, from their associated entry zones into the spinal cord. This leads to the production of deafferentation pain in up to 20% to 30% of patients with brachial plexus injuries.36 Brachial plexus avulsion pain may begin immediately after the trauma, but its onset can also occur months to years later. Pain projection depends primarily on the extent of the injury and the number of avulsed roots involved; it may include the whole upper limb but usually radiates to the forearm and hand.
Multiple groups have extensive experience with the application of DREZ lesions to treat pain from brachial plexus avulsion injury. Sindou and coauthors reported that 42% of patients had complete avulsion of all plexus roots; they also noticed scarring, arachnoiditis, and atrophy of the spinal cord, which in some cases was rotated. They reported that 66% of patients had good to excellent outcomes, with 71% demonstrating an improvement in daily activities (mean follow-up was 6 years).37 Friedman and colleagues reported similar results: 77% of patients had a 75% reduction in pain intensity.38,39 Prestor reported that 47.6% of patients had complete resolution of pain whereas 80.9% had at least 70% improvement. He noticed that better results were obtained in patients who underwent surgery more than 1 year after injury and reported poor results in patients previously treated with pain management surgery such as cordotomy or myelotomy.11 In a long-term follow-up study, Chen and associates reported early good results in 80% of patients operated on by thermocoagulation; however, this number dropped to 60% (5-year follow-up) and 50% (10-year follow-up).40,41 Samii and colleagues reported a 50% reduction in pain in 86% of patients immediately postoperatively, in 68% after 3 months, in 63% after 6 months, and in 62% in long-term follow-up. They found no correlation between the number of roots avulsed or the extent of the DREZ coagulation procedure performed and the degree of pain reduction, between the duration of pain and outcome after DREZ, or between pain onset and time to surgery.42 Dreval applied ultrasound to perform DREZ lesioning and operated on 127 patients. He reported that 96% of patients had immediate improvement and 87% had a good result at follow-up (average follow-up of 47.5 months).19
Spinal Cord Injury Pain
The incidence of all types of chronic pain after SCI has been variously reported to be between 18% and 94%.43–45 This variability would seem to be dependent on the population surveyed, the survey method, and pain types included (mild and moderate). An incidence of pain of around 65% after SCI is a good first approximation.46 In a longitudinal study of the prevalence and characteristics of pain in the first 5 years after SCI, Siddall and associates found that musculoskeletal pain was the most commonly experienced type of pain (59%).47
Reports vary on the incidence of neuropathic pain after SCI, with estimates varying between 10% and 25%.33,48,49 Pain may occur immediately after injury or be delayed for several years and usually has a burning character.50,51 Neuropathic pain after SCI has been divided into “at level” and “below level.” The incidence of at-level and below-level neuropathic pain has variously been reported to be 13% to 51% and 27% to 42%, respectively, after SCI.47,52 Werhagen and coauthors reported that the incidence of neuropathic injury pain is lower in younger patients (26% in patients younger than 20 years at time of injury versus 58% in patients older than 20 years). Furthermore, below-level pain is more common in SCI patients younger than 40 years, whereas at-level pain is more prevalent in patients older than 40 years at the time of injury.47,52
Sindou and associates reported good long-term results in 65% of patients with segmental pain and 0% improvement in those with infrasegmental pain. A good result was obtained in 88% of patients with predominantly paroxysmal pain, whereas only 26% with continuous pain had good results.31 Nashold and Bullitt reported good results in 77%,50 whereas Sampson and coworkers reported that 54% of patients were pain free after 3 years’ follow-up and noted better results in patients with incomplete injuries.53 Richter and Seitz reported good results with DREZ lesions in the cervical spinal cord for brachial plexus avulsion and poor results in paraplegic patients with infrasegmental pain; patients with cervical pain experienced a 30% recurrence rate.54 Kanpolat and coauthors reported good results in 47% of patients with segmental pain.30 Friedman and Nashold reported a 50% improvement over a 6-month to 6-year interval in patients with segmental pain rather than diffuse pain.39
Selection of patients for DREZ lesions is critical in those with SCI pain. Studies such as the ones just cited have shown that patients with pain in the segmental region after spinal cord trauma experience a better response than do those who have diffuse pain or pain that is below the injured segment.30,31,38,51,55 Caution should be exercised when performing DREZ lesions in patients with incomplete SCI to avoid aggravation of weakness by performance of an overly deep or aggressive lesion. In the case of complete SCI, a deep lesion can, of course, be more safely performed.
Phantom Limb Pain
Good results have been reported when the pain has a paroxysmal character or allodynia (perception of pain from what would ordinarily be a nonpainful stimulus) is a prominent feature. Good results can also be achieved in posttraumatic cases.51 Patients with phantom limb pain who also have nerve root avulsion may also have good results. Stump pain is not usually relieved unless it is of a paroxysmal type.11 Saris and colleagues operated on patients with pain from a phantom limb secondary to trauma, gangrene, and cancer and reported complete relief of the pain in 36%.56 Malin and Winkelmuller also reported good results in patients with peripheral nerve injuries that were associated with root avulsion.57
