A Systematic Literature Review of Dorsal Root Ganglion Neurostimulation for the Treatment of Pain.

OBJECTIVE: To conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain. DESIGN: Grade the evidence for DRG stimulation. METHODS: An international, interdisciplinary work group conducted a literature search for DRG stimulation. Abstracts were reviewed to select studies for grading. General inclusion criteria were prospective trials (randomized controlled trials and observational studies) that were not part of a larger or previously reported group. Excluded studies were retrospective, too small, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria. RESULTS: DRG stimulation has Level II evidence (moderate) based upon one high-quality pivotal randomized controlled trial and two lower-quality studies. CONCLUSIONS: Moderate-level evidence supports DRG stimulation for treating chronic focal neuropathic pain and complex regional pain syndrome.

A Systematic Literature Review of Spine Neurostimulation Therapies for the Treatment of Pain.

OBJECTIVE: To conduct a systematic literature review of spinal cord stimulation (SCS) for pain. DESIGN: Grade the evidence for SCS. METHODS: An international, interdisciplinary work group conducted literature searches, reviewed abstracts, and selected studies for grading. Inclusion/exclusion criteria included randomized controlled trials (RCTs) of patients with intractable pain of greater than one year's duration. Full studies were graded by two independent reviewers. Excluded studies were retrospective, had small numbers of subjects, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria. RESULTS: SCS has Level 1 evidence (strong) for axial back/lumbar radiculopathy or neuralgia (five high-quality RCTs) and complex regional pain syndrome (one high-quality RCT). CONCLUSIONS: High-level evidence supports SCS for treating chronic pain and complex regional pain syndrome. For patients with failed back surgery syndrome, SCS was more effective than reoperation or medical management. New stimulation waveforms and frequencies may provide a greater likelihood of pain relief compared with conventional SCS for patients with axial back pain, with or without radicular pain.

Discitis Following Radiofrequency Nucleoplasty: A Case Report.

INTRODUCTION: Radiofrequency nucleoplasty is a minimally invasive procedure to treat chronic low back pain, especially mild degenerative disc diseases. Discitis after radiofrequency nucleoplasty is a rare case. CASE PRESENTATION: A 62-year-old male patient with a chief complaint of 10 years low back pain, gradually worsening for the last two years, a history of hypertension, chronic kidney disease, and routine dialysis twice a week, referred to the center. He underwent a lumbar medial branch block using radiofrequency and radiofrequency nucleoplasty procedure of lumbar 4-5 (L4-L5). Three weeks after the intervention, he could not move his legs, associated with urinary and fecal incontinence. MRI (magnetic resonance imaging) of the lumbar spine was performed, and the results indicated hyperintensity in L4-L5, suspicious of discitis. Laminectomy at L4 and L5 was performed. Eight months after surgery, the patient could feel and lift legs, and urinary and fecal incontinence was also controlled. CONCLUSIONS: Early diagnosis of discitis is critical and challenging. Delay in diagnosis may lead to treatment delay and the development of neurological deficits. Comprehensive treatment with bed rest, antimicrobial therapy, and sensible application of timely surgery are essentials to an optimal outcome.

Effectiveness and Safety of Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pain: A Pooled Analysis.

INTRODUCTION: Since it became available in the mid-2010s, dorsal root ganglion (DRG) stimulation has become part of the armamentarium to treat chronic pain. To date, one randomized controlled trial, and several studies of moderate sample size and various etiologies have been published on this topic. We conducted a pooled analysis to investigate the generalizability of individual studies and to identify differences in outcome between chronic pain etiologic subgroups and/or pain location. MATERIALS AND METHODS: One prospective, randomized comparative trial and six prospective, single-arm, observational studies were identified that met pre-defined acceptance criteria. Pain scores and patient-reported outcome (PRO) measures were weighted by study sample sizes and pooled. Safety data are reported in aggregate form. RESULTS: Our analysis included 217 patients with a permanent implant at 12-month follow-up. Analysis of pooled data showed an overall weighted mean pain score of 3.4, with 63% of patients reporting ≥50% pain relief. Effectiveness sub-analyses in CRPS-I, causalgia, and back pain resulted in a mean reduction in pain intensity of 4.9, 4.6, and 3.9 points, respectively. Our pooled analysis showed a pain score for primary affected region ranging from 1.7 (groin) to 3.0 (buttocks) and responder rates of 80% for foot and groin, 75% for leg, and 70% for back. A substantial improvement in all PROs was observed at 12 months. The most commonly reported procedural or device complications were pain at the IPG pocket site, lead fracture, lead migration, and infection. CONCLUSIONS: DRG stimulation is an effective and safe therapy for various etiologies of chronic pain.

Evaluating Dorsal Root Ganglion Stimulation in a Prospective Dutch Cohort.

OBJECTIVES: Dorsal root ganglion (DRG) stimulation is a recent neuromodulation option that has delivered safe, effective pain relief for a number of etiologies. This prospective observational study was intended to establish the effectiveness of this treatment in a typical real-world clinical context. MATERIALS AND METHODS: Participants with chronic, intractable pain of the trunk or lower limbs were recruited from multiple pain clinics in the Netherlands. Subjects were trialed and implanted with DRG stimulation systems. Pain, function, mood, and quality of life, ratings were collected through 12 months postimplant. RESULTS: Of the 66 subjects enrolled, failed back surgery syndrome, peripheral nerve injury, and complex regional pain syndrome formed the largest etiologies. Permanent implants were placed in 86.2% subjects (56/65). After 12 months of treatment, average pain ratings in subjects' primary area of pain decreased from 8.0 cm at baseline to 4.1 cm, and 49% of subjects had ≥50% reduction in pain (visual analog scale). In addition, functional capacity was increased, and mood and quality of life improved. No confirmed lead migrations were observed, and there was a low rate of infection. CONCLUSIONS: DRG stimulation significantly reduced the severity of subjects' pain and enabled participatory changes that improved quality of life through 12-months postimplant.

The Neuromodulation Appropriateness Consensus Committee on Best Practices for Dorsal Root Ganglion Stimulation.

INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) is dedicated to improving the safety and efficacy of neuromodulation and thus improving the lives of patients undergoing neuromodulation therapies. With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion (DRG) stimulation has significantly improved the treatment of complex regional pain syndrome (CRPS), among other conditions. Through funding and organizational leadership by the International Neuromodulation Society (INS), the NACC reconvened to develop the best practices consensus document for the selection, implantation and use of DRG stimulation for the treatment of chronic pain syndromes. METHODS: The NACC performed a comprehensive literature search of articles about DRG published from 1995 through June, 2017. A total of 2538 article abstracts were then reviewed, and selected articles graded for strength of evidence based on scoring criteria established by the US Preventive Services Task Force. Graded evidence was considered along with clinical experience to create the best practices consensus and recommendations. RESULTS: The NACC achieved consensus based on peer-reviewed literature and experience to create consensus points to improve patient selection, guide surgical methods, improve post-operative care, and make recommendations for management of patients treated with DRG stimulation. CONCLUSION: The NACC recommendations are intended to improve patient care in the use of this evolving therapy for chronic pain. Clinicians who choose to follow these recommendations may improve outcomes.

Retrospective Case Series on the Treatment of Painful Diabetic Peripheral Neuropathy With Dorsal Root Ganglion Stimulation.

BACKGROUND: The dorsal root ganglion (DRG) has been identified as an important neural structure in the development and maintenance of chronic pain. We present a retrospective case series of patients with refractory painful diabetic peripheral neuropathy (PDPN) that underwent electrical stimulation of the DRG and report on changes in their overall perceived pain and complication rates. METHODS: Ten diabetic males (mean age 65.2 [SD 8.8] years) with painful symptoms of the lower limbs were enrolled and trialed with up to four quadripolar percutaneous DRG stimulation leads between L2 and L5 spinal levels. Patients received a fully implantable neurostimulation system (Abbott Laboratories, Sunnyvale, CA, USA) immediately or after a successful trial period (>50% reduction in pain). Overall perceived pain was measured by visual analogue scale (VAS) at baseline, one-week postimplantation and one-, three-, six-, and twelve-month follow-up (n = 5). RESULTS: Ten patients were included in this retrospective study. Seven of these subjects received permanent stimulator implants after successful externalized or intraoperative trials. Two of those patients subsequently required explantation, due to failure to capture primary pain area (n = 1) and personal reasons (n = 1). For the five subjects that proceeded to clinical follow-ups, baseline VAS was reduced by an average of 63.90% (SD 21.39; p < 0.001) postimplantation. For four patients with available 12-month follow-up data, mean relative reduction in overall perceived pain averaged 64.16% (SD 35.8; p< 0.001). CONCLUSION: Early findings from this small retrospective case series, suggest DRG is a safe and effective neuromodulation modality to improve painful symptoms in PDPN patients. Future prospective trials are required to further investigate the use of DRG stimulation for this clinical indication.

Stimulation of the L2-L3 Dorsal Root Ganglia Induces Effective Pain Relief in the Low Back.

INTRODUCTION: Chronic low back pain affects millions of people worldwide and can arise through a variety of clinical origins. In the case of failed back surgery syndrome (FBSS), previous surgical procedures can contribute to low back pain that is often unresponsive to intervention. Although spinal cord stimulation (SCS) can be an effective treatment modality, it does not provide sufficient pain relief for some intractable cases. Recently, alternative neuromodulation options have been developed, including dorsal root ganglion (DRG) stimulation. The objective of this report is to further investigate these clinical observations. METHODS: Twelve patients with significant chronic discogenic low back pain due to FBSS were included. All subjects underwent implantation of DRG stimulation systems that had at least 1 lead placed at L2 or L3. Subjects' pain ratings, mood, and quality of life were tracked prospectively for up to 12 months. RESULTS: More than half of subjects reported 50% or better pain relief in the low back, and the average low back pain relief was 45.5% at 12 months. Concomitant reductions in overall pain, leg pain, pain interference, mood, and quality of life were also found. DISCUSSION: For the studied population, DRG stimulation at the L2-L3 levels was effective at relieving low back pain. These reductions in pain were associated with improvements in quality of life. Thus, DRG stimulation at these levels may be effective for low back pain by recruiting both segmental and nonsegmental neural pathways that are not otherwise accessible via traditional SCS.

The Dorsal Root Ganglion as a Therapeutic Target for Chronic Pain.

Chronic neuropathic pain is a widespread problem with negative personal and societal consequences. Despite considerable clinical neuroscience research, the goal of developing effective, reliable, and durable treatments has remained elusive. The critical role played by the dorsal root ganglion (DRG) in the induction and maintenance of chronic pain has been largely overlooked in these efforts, however. It may be that, by targeting this site, robust new options for pain management will be revealed. This review summarizes recent advances in the knowledge base for DRG-targeted treatments for neuropathic pain:• Pharmacological options including the chemical targeting of voltage-dependent calcium channels, transient receptor potential channels, neurotrophin production, potentiation of opioid transduction pathways, and excitatory glutamate receptors.• Ablation or modulation of the DRG via continuous thermal radiofrequency and pulsed radiofrequency treatments.• Implanted electrical neurostimulator technologies.• Interventions involving the modification of DRG cellular function at the genetic level by using viral vectors and gene silencing methods.

Management of Postherniorrhaphy Chronic Neuropathic Groin Pain: A Role for Dorsal Root Ganglion Stimulation.

Chronic neuropathic groin pain is a sequela of hernia surgery that occurs at unacceptably high rates, causing widespread impacts on quality of life. Although the medical community is beginning to recognize the role of surgical technique in the initiation and maintenance of postherniorrhaphy neuropathic pain, little information exists regarding pain management strategies for this condition. This review presents a summary of the pain condition state, its treatment options, and treatment recommendations. Both literature review and clinical experience were used to develop a proposed a treatment algorithm for the treatment of postherniorrhaphy pain. The development of chronic pain may be prevented via a number of perioperative measures. For pain that is already established, some surgical approaches including inguinal neurectomy can be effective, in addition to standard pharmacological treatments and local infiltrations. An unmet need may still exist with these options, however, leaving a role for neuromodulation for the treatment of intractable cases. A pain management algorithm for iterative interventions including stimulation of the dorsal root ganglion (DRG) is described. It is expected that cross-disciplinary awareness of surgeons for nonsurgical pain management options in the treatment of chronic neuropathic postherniorrhaphy pain will contribute to better clinical outcomes.

Stimulation of the Dorsal Root Ganglion.

Dorsal root ganglion (DRG) stimulation has recently emerged as a new neuromodulation modality that stays on the intersection of the peripheral and central nervous system. With DRG location within the spinal column and with electrodes for DRG stimulation placed through the intraspinal epidural space, it may make more sense to group DRG stimulation together with more commonly used spinal cord stimulation (SCS) rather than peripheral nerve stimulation (PNS), particularly if one agrees that the stimulation delivered to DRG partly works downstream at the spinal cord level. Based on current experience, it appears that DRG stimulation of the spinal cord is as effective as SCS in relieving various neuropathic pain syndromes including pain due to failed back surgery syndrome, complex regional pain syndromes, and chronic postsurgical pain. In addition to its efficacy, DRG stimulation of the spinal cord is associated with a lower rate of migrations and lack of positional side effects that may be seen with SCS and PNS. Here we summarize the knowledge base and clinical evidence for DRG stimulation of the spinal cord, and present hypotheses of its mechanism of action.

One-year outcomes of spinal cord stimulation of the dorsal root ganglion in the treatment of chronic neuropathic pain.

OBJECTIVES: Spinal cord stimulation of the dorsal root ganglion (DRG-SCS) is a new therapy for treating chronic neuropathic pain. Previous work has demonstrated the effectiveness of DRG-SCS for pain associated with failed back surgery syndrome, complex regional pain syndrome, chronic postsurgical pain, and other etiologies through 6 months of treatment; this report describes the maintenance of pain relief, improvement in mood, and quality of life through 12 months. MATERIALS AND METHODS: Subjects with intractable pain in the back and/or lower limbs were implanted with an active neurostimulator device. Up to four percutaneous leads were placed epidurally near DRGs. Subjects were tracked prospectively for 12 months. RESULTS: Overall, pain was reduced by 56% at 12 months post-implantation, and 60% of subjects reported greater than 50% improvement in their pain. Pain localized to the back, legs, and feet was reduced by 42%, 62%, and 80%, respectively. Measures of quality of life and mood were also improved over the course of the study, and subjects reported high levels of satisfaction. Importantly, excellent pain-paresthesia overlap was reported, remaining stable through 12 months. DISCUSSION: Despite methodological differences in the literature, DRG-SCS appears to be comparable to traditional SCS in terms of pain relief and associated benefits in mood and quality of life. Its benefits may include the ability to achieve precise pain-paresthesia concordance, including in regions that are typically difficult to target with SCS, and to consistently maintain that coverage over time.

Lack of body positional effects on paresthesias when stimulating the dorsal root ganglion (DRG) in the treatment of chronic pain.

OBJECTIVES: One prominent side effect from neurostimulation techniques, and in particular spinal cord stimulation (SCS), is the change in intensity of stimulation when moving from an upright (vertical) to a recumbent or supine (horizontal) position and vice versa. It is well understood that the effects of gravity combined with highly conductive cerebrospinal fluid provide the mechanism by which changes in body position can alter the intensity of stimulation-induced paresthesias. While these effects are well established for leads that are placed within the more medial aspects of the spinal canal, little is known about these potential effects in leads placed in the lateral epidural space and in particular within the neural foramina near the dorsal root ganglion (DRG). MATERIALS AND METHODS: We prospectively validated a newly developed paresthesia intensity rating scale and compared perceived paresthesia intensities when subjects assumed upright vs. supine bodily positions during neuromodulation of the DRG. RESULTS: On average, the correlation coefficient between stimulation intensity (pulse amplitude) and perceived paresthesia intensity was 0.83, demonstrating a strong linear relationship. No significant differences in paresthesia intensities were reported within subjects when moving from an upright (4.5 ± 0.14) to supine position 4.5 (± 0.12) (p > 0.05). This effect persisted through 12 months following implant. CONCLUSIONS: Neuromodulation of the DRG produces paresthesias that remain consistent across body positions, suggesting that this paradigm may be less susceptible to positional effects than dorsal column stimulation.

Spinal cord stimulation of the dorsal root ganglion for groin pain-a retrospective review.

BACKGROUND: Spinal cord stimulation (SCS) is a standard treatment option for chronic neuropathic pain. However, some anatomical pain distributions are known to be difficult to cover with traditional SCS-induced paresthesias and/or may also induce additional, unwanted stimulation. We present the results from a retrospective review of data from patients with groin pain of various etiologies treated using neuromodulation of the dorsal root ganglion (DRG). METHODS: Data from 29 patients with neuropathic groin pain were reviewed. Patients underwent trial therapy where specifically designed leads were implanted at the target DRGs between T12 and L4. Patients who had a successful trial (> 50% improvement) received the fully implantable neuromodulation system. Pain scores were captured on a visual analog scale (VAS) at baseline and at regular follow-up visits. RESULTS: Twenty-five patients (86.2%) received fully implantable neurostimulators, and the average follow-up period was 27.8 ± 4.3 (standard error of the mean, SEM) weeks. The average pain reduction was 71.4 ± 5.6%, and 82.6% (19/23) of patients experienced a > 50% reduction in their pain at the latest follow-up. Individual cases showed improvement with a variety of etiologies and pain distributions; a subanalysis of postherniorrhaphy cohort also showed significant improvement. CONCLUSIONS: Early findings suggest that neuromodulation of the DRG may be an effective treatment for chronic neuropathic pain conditions in the groin region. This technique offers a useful alternative for pain conditions that do not always respond optimally to traditional SCS therapy. Neuromodulation of the DRG provided excellent cross-dermatomal paresthesia coverage, even in cases with patients with discrete pain areas. The therapy can be specific, sustained, and independent of body position.

Stimulation of dorsal root ganglia for the management of complex regional pain syndrome: a prospective case series.

BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic and progressive pain condition usually involving the extremities and characterized by sensorimotor, vascular, and trophic changes. Spinal cord stimulation (SCS) is an effective intervention for this condition, but is hampered by the technical challenges associated with precisely directing stimulation to distal extremities. Dorsal root ganglia (DRG) may be more effective as a physiological target for electrical modulation due to recruitment of the primary sensory neurons that innervate the painful distal anatomical regions. METHODS: Eleven subjects diagnosed with uni- or bilateral lower-extremity CRPS were recruited as part of a larger study involving chronic pain of heterogeneous etiologies. Quadripolar epidural leads of a newly developed neurostimulation system were placed near lumbar DRGs using conventional percutaneous techniques. The neurostimulators were trialed; 8 were successful and permanently implanted and programed to achieve optimal pain-paresthesia overlap. RESULTS: All 8 subjects experienced some degree of pain relief and subjective improvement in function, as measured by multiple metrics. One month after implantation of the neurostimulator, there was significant reduction in average self-reported pain to 62% relative to baseline values. Pain relief persisted through 12 months in most subjects. In some subjects, edema and trophic skin changes associated with CRPS were also mitigated and function improved. Neuromodulation of the DRG was able to provide excellent pain-paresthesia concordance in locations that are typically hard to target with traditional SCS, and the stimulation reduced the area of pain distributions. CONCLUSIONS: Neuromodulation of the DRG appears to be a promising option for relieving chronic pain and other symptoms associated with CRPS. The capture of discrete painful areas such as the feet, combined with stable paresthesia intensities independent of body position, suggests this stimulation modality may allow more selective and consistent targeting of painful areas than traditional SCS.

The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. METHODS: The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. RESULTS: Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated. CONCLUSIONS: Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation.

The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain. Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes. METHODS: The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks. RESULTS: The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician. CONCLUSIONS: The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly.

The appropriate use of neurostimulation: new and evolving neurostimulation therapies and applicable treatment for chronic pain and selected disease states. Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need to provide an expert consensus that defines the appropriate use of neuromodulation technologies for appropriate patients. The Neuromodulation Appropriateness Consensus Committee (NACC) was formed to give guidance to current practice and insight into future developments. METHODS: The INS executive board selected members of the international scientific community to analyze scientific evidence for current and future innovations and to use clinical experience to fill in any gaps in information. The NACC used PubMed and Google Scholar to obtain current evidence in the field and used clinical and research experience to give a more complete picture of the innovations in the field. RESULTS: The NACC has determined that currently approved neurostimulation techniques and technologies have expanded our ability to treat patients in a more effective and specific fashion. Despite these advances, the NACC has identified several additional promising technologies and potential applications for neurostimulation that could move this field forward and expand the applicability of neuromodulation. CONCLUSIONS: The NACC concludes that the field of neurostimulation is an evolving and rapidly changing one that will lead to improved patient access, safety, and outcomes.