Dorsal Root Ganglion Stimulation for Pain Control

Abstract

The dorsal root ganglion (DRG) is a novel neuromodulation target. In the 5 years since the introduction of a DRG stimulation system, international evidence has demonstrated its clinical effectiveness, precision of targeting, and stability of therapy and paresthesias. In a recent groundbreaking randomized controlled trial, DRG stimulation was demonstrated to be statistically superior to tonic spinal cord stimulation (SCS) in the management of lower-extremity complex regional pain syndrome. In this chapter we discuss the neurological and clinical rationale for DRG stimulation and review the key literature for this intervention.

Because the implantation of leads at the DRG is more complex than the placement of leads over the dorsal columns of the spinal cord when performing SCS, we provide a detailed overview of the surgical procedures necessary to deploy a DRG stimulation system. It is anticipated that these descriptions will expand the understanding of this intervention.

Keywords

Dorsal root ganglion, Minimally invasive, Neuropathic pain, Neurostimulation, Pain management, Percutaneous

Outline
Dorsal Root Ganglion Stimulation: The Intervention 683
- The DRG’s Role in Pain 683
- DRG Stimulation 684
Implantation: Surgical Considerations 684
- Preimplantation Planning 684
- Lead Implantation 685
- Securing the Leads 686
- Trial Period Options 686
- INS Placement 688
- Programming 688
- Follow-up 688
Outcomes 689
- The European Experience 689
- The Australian Experience 690
- Worldwide Experience 690
Conclusions 691
Acknowledgments [CR]
Conflict of Interest Statement 691
References 691

Acknowledgments

The author thanks Allison Foster, PhD, an independent medical writer on the author’s staff, for her intellectual contribution to the drafting of the manuscript.

Conflict of Interest Statement

Dr. Verrills is a shareholder of Clinical Intelligence Pty Ltd., and a peer-to-peer teacher and consultant to both Nevro Corp. and St. Jude Medical Inc.

Dorsal Root Ganglion Stimulation: The Intervention

The pain management perspective for treating chronic neuropathic pain exists on a continuum of care. Best practice involves multidisciplinary collaboration between the pain management consultant(s), psychologist, neurologist, and physiotherapist in communication with the referring physician. Pain management therapy should be selected on the overlapping principles of safety, appropriateness, fiscal neutrality, and effectiveness (SAFE) ( ). In cases where neuropathic pain is intractable to conventional approaches, neuromodulation via implanted devices for electrical stimulation can be employed at a number of nervous system levels, including the brain, intraspinal sites, and in the periphery. The dorsal root ganglion (DRG) is an emerging target for neuromodulation in the spine. The challenges that are inherent to DRG stimulation when using stiff conventional spinal cord stimulation (SCS) leads/electrodes with large contacts and wide intercontact spacing ( ) have been addressed by the development of a specialized DRG stimulation system (Axium, St. Jude Medical, St. Paul, MN, USA).

The DRG’s Role in Pain

The DRG is located inside the dural capsule in the lateral vertebral foramen in the spinal canal. It is a bilateral bulbous structure on the dorsal roots and houses the cell bodies and proximal processes of primary sensory neurons (PSNs) as well as satellite glial cells (SGCs) and immune cells ( ). PSNs are pseudounipolar cells; their dendrites, located throughout the body, transmit action potentials (APs) toward the central nervous system (CNS) and pass the T-junction of the DRG (the point at which the peripheral and central dendrites bifurcate from the process that extends from the soma) along the way. Depending on levels of activity and cellular conditions, the T-junction may function as a filter that restricts some APs from reaching the spinal cord or may enhance/propagate peripheral activity due to the intrinsic activity arising from the DRG itself ( ). Each DRG is somatotopically organized ( ), with up to 15,000 cell bodies per DRG at segmental levels where a major plexus innervates limbs ( ). Each DRG subserves sensory information specific to that spinal level in an approximately dermatomal fashion, although considerable cross-linkages and functional overlap exist between DRGs at adjacent spinal levels ( ).

The pathological events leading to neuropathic pain often begin with peripheral injury at the sensory nerve. The PSNs respond with pathological changes, including increased receptor expression, increased membrane excitability, and repetitive ectopic firing originating in the DRG ( ). The hyperexcitable state of DRG sensory neurons may be caused by the loss of inward calcium currents, alterations in sodium channels, and release of intracellular second messengers ( ). At projection sites within the spinal cord and elsewhere in the CNS there is increased release of excitatory amino acids and other neurotransmitters and signaling molecules, the functional consequence of which may be long-term potentiation and central sensitization. Other cellular populations may also be activated, as there is proliferation among SGCs in the DRG and microglia in the spinal cord, and sympathetic fiber baskets sprout around PSN somata ( ). Thus the DRG area is an important neuromodulation target because it plays a pivotal role in the development and maintenance of chronic pain. For a more complete discussion of the role of the DRG in the development of chronic neuropathic pain see ).

DRG Stimulation

Electrical stimulation reduces the ectopic firing rate of in vitro DRG neurons ( ). It is thought that the clinical pain-relieving effect of DRG stimulation is achieved by a similar mechanism, in which the overactivity/hypersensitivity of the DRG is reversed by exogenous electrical pacing ( ).

Stimulation of the DRG can be achieved via a minimally invasive epidural approach. Because the DRG is located within the vertebral canal and can be identified on the basis of landmarks such as the vertebral pedicles ( ), small flexible leads can be navigated through the intraforaminal ligaments and placed consistently near the DRG. The relative lack of cerebrospinal fluid around the DRG allows for increased energy efficiency, so DRG stimulation uses approximately 15% of the power consumption of tonic SCS systems ( ). The bony enclosures around the DRG ensure that the relationship between the lead and DRG remains constant, i.e., the strength of electrical field on neural tissue remains constant despite changes in bodily position and gravitational effects ( ).

The outcomes of DRG stimulation are different from those of SCS in regards to the distributions of paresthesia that can be generated. SCS generally covers broad swathes of the body and can be more easily directed to the limbs than the trunk. DRG stimulation, on the other hand, is generally characterized by smaller subdermatomal coverage patterns that can be readily applied to both axial and radicular pain distributions. It is theorized that DRG stimulation preferentially recruits the PSNs that have altered membrane properties due to neuropathological pain-initiated changes, given that the threshold for firing is halved in a genetic mutation animal model of chronic pain ( ). This selectivity may be responsible for the localized treatment that is possible with DRG stimulation. Contrast this with SCS, in which broad regions of the dorsal columns, including fibers which may or may not play a role in pain perception, are stimulated to create broad paresthesias ( ). Thus DRG stimulation may allow direct and specific modulation of algogenic sites.

Implantation: Surgical Considerations

Preimplantation Planning

Criteria for patient selection have been discussed previously ( ). Briefly, patients who suffer from nonsurgically remediable chronic neuropathic pain of the trunk or limbs are candidates. Common pain etiologies that are amenable to treatment with DRG stimulation include complex regional pain syndrome (CRPS), causalgia, failed back surgery syndrome (FBSS), and peripheral neuropathies secondary to trauma or surgery. DRG stimulation leads can be placed at cervical, thoracic, and lumbar sites, but regulatory approval in the United States by the Food and Drug Administration (FDA) specifies placement between T10 and S2 levels. Patients with axial pain conditions, such as primary neuropathic low back pain or groin pain, and those with localized complaints such as postarthroscopic neuropathic knee pain can also be considered candidates for DRG stimulation.

The patient’s condition and medical and surgical history should be carefully reviewed. Spinal abnormalities or previous posterior back surgeries near the target vertebrae/foramen may complicate epidural lead placement, so lateral X-rays and magnetic resonance imaging (MRI) of the lumbar spine should be considered to assess the degree of foraminal stenosis. In cases where stenosis is moderate or severe, SCS or peripheral nerve stimulation (PNS) may be more appropriate. The presence of standard contraindications to surgery or implantation of an active device (such as medical comorbidities and an ongoing need for MRI or diathermy) would exclude DRG stimulation placement. Prophylactic antibiotics are prescribed at the discretion of the physician. Target DRGs are identified clinically based on the affected/painful dermatome(s) or via preoperative retrograde transforaminal paresthesia mapping ( ).

In the operating theater, patients should be placed prone with a pillow under the hips or sternum to reduce lordosis of the spine and open the interlaminar spaces between vertebral bodies to assist with gaining epidural access. Light sedation in addition to local anesthesia is indicated. Prior to draping the patient, the target vertebrae are identified under anterior–posterior fluoroscopy and the inferior angle of the pedicle marked on the skin. The midline epidural entry point, one vertebral level below this mark over the inferior angle of the pedicle, is marked on the skin. The skin entry point, another one or two vertebral levels below and oriented at the contralateral pedicles, is also marked. A straight-line trajectory for the needle is marked from the skin entry point through the midline epidural entry point to the target pedicle (see Fig. 53.1 ). It should be noted that a needle trajectory that is too obtuse may result in excessive resistance being encountered at the entry to the foramina, with lead buckling; while a needle trajectory that is too paramedian can result in great difficulties navigating the curve into the dorsal aspect of the foramen and it is likely to slip in a cephalic manner medial to the pedicle.

Lead Implantation

After a small cutaneous incision is made with a surgical blade stab, the needle is advanced along the previously marked pathway through the ligamentum flavum, ensuring (via fluoroscopy if needed) that the needle tip is on the midline and pointing toward the targeted pedicle. Epidural access is gained through the standard loss of resistance technique. The needle should be oriented at 30–40 degrees relative to the plane of the patient’s back to ensure dorsal placement of the leads (see Fig. 53.2 ). Steep needle angle can make lead placement difficult in the lumbar spine, although it is noted that steeper approaches are required as one moves more cephalad in the body for thoracic or cervicothoracic junction placements. The port flush and needle bevel must be oriented cranially.

The delivery system (the curved sheath, guidewire, locking hub, lead, and stylet) is then prepared. A delivery sheath is selected; the wide curve is used for most initial approaches, while the narrow curve is more appropriate for instances where a more obtuse angle of needle trajectory is used, i.e., at the L5/S1 interspace. The guidewire is loaded into the selected delivery sheath until its tip protrudes slightly from the end, and the lead stabilizer hub is tightened to fasten it in place. The sheath/guidewire combination is then inserted into the epidural needle and advanced into the epidural space. The needle and sheath/guidewire are rotated together to face the most dorsal aspect of the foramina of interest and guided toward it under live fluoroscopy; the distal end of the sheath has a radiopaque band for visualization. The sheath/guidewire should first contact the inferior aspect of the targeted pedicle and then brush past it and the intraforaminal ligaments to enter the spinal foramina. Some mild resistance is normal, and gentle maneuvering can be used to pass through the ligaments. The lead stabilizer hub is then loosened and the guidewire is removed while maintaining the delivery sheath in situ. The lead, with the stylet inserted for stability, is then loaded into the delivery sheath and pushed forward to its tip. The lead is deployed at the DRG while simultaneously retracting the delivery sheath slightly; it is usual to retract it about 1 cm or to approximately the inferior vertebral endplate. The ideal final position for the lead is along the dorsal aspect of the foramina with the second and third electrode contacts straddling the pedicle (see Fig. 53.3 ).