Dorsal Root Ganglion Stimulation for Chronic Pelvic Pain: A Case Series and Technical Report on a Novel Lead Configuration

Lower urinary tract (LUT) dysfunction arising from injury and disease remain a clinical challenge due to unavailability of pharmacological treatments. Neuromodulation devices developed to tackle these disorders, such as sacral stimulators, are non‐selective for a single nerve with numerous off‐target effects while also stimulating the afferent and efferent population in a nerve. Here, we investigate whether epidural spinal cord stimulation (SCS) and microstimulation of dorsal root ganglion (DRG) through penetrating microarrays, can selectively activate and control reflexes relevant to LUT function. We demonstrate that custom high‐density epidural arrays and Utah arrays in the DRG can selectively access pelvic and pudendal innervation, and can modulate LUT function.To determine the effects of stimulation on peripheral nerve recruitment, α‐chloralose anesthetized male cats (SCS: n=6, DRG: n=4) were instrumented with nerve cuffs on the pelvic nerve as well as the pudendal nerve and its branches. High‐density epidural electrodes were placed corresponding to the lumbosacral (L6 and L7 laminae) and sacral (S1 laminae) spinous processes. In separate DRG experiments, 32‐channel high‐density penetrating Utah arrays were implanted in the S1, S2 and S3 DRG. We stimulated epidurally and within the DRG while recording compound action potentials in nerve cuffs. Functional effects of stimulation were measured using intravesical and transurethral catheters to measure bladder and urethral pressures respectively across various stimulus amplitudes and frequencies.All the instrumented nerves could be selectively recruited with both DRG and SCS stimulation, although not every nerve was selectivity recruited in every animal. The stimulation amplitude to evoke functional responses was higher (SCS: 600–1000 μA, DRG: 20–45 μA) than the minimum threshold to evoke antidromic activity in nerve cuffs. SCS and DRG stimulation both evoked bladder parasympathetic contractions similar to direct stimulation of the pelvic nerve. In several trials, stimulation through the same epidural electrode during cystometry, low frequency (3 Hz) stimulation evoked a continence reflex resulting in a suppression of detrusor activity, while high frequency (33 Hz) stimulation evoked a micturition reflex resulting in high intravesical pressures. Isovolumetric and filling cystometry was performed to confirm the action of these reflexes.SCS and DRG stimulation can selectively activate pelvic and pudendal innervation, and elicit micturition and continence reflexes.Support or Funding InformationR01 NS088184 and OT2OD024908. Craig H. Neilsen Foundation Award 476681

Background: Spinal cord stimulation is an intervention that has become increasingly popular due to the growing body of literature showing its effectiveness in treating pain and the reversible nature of the treatment with implant removal. It is currently approved by the FDA for chronic pain of the trunk and limbs, intractable low back pain, leg pain, and pain from failed back surgery syndrome. In Europe, it has additional approval for refractory angina pectoris and peripheral limb ischemia. Objective: This narrative review presents the current evidence supporting the use of spinal cord stimulation for the approved indications and also discusses some emerging neuromodulation technologies that may potentially address pain conditions that traditional spinal cord stimulation has difficulty addressing. Study Design: Narrative review. Results: Spinal cord stimulation has been reported to be superior to conservative medical management and reoperation when dealing with pain from failed back surgery syndrome. It has also demonstrated clinical benefit in complex regional pain syndrome, critical limb ischemia, and refractory angina pectoris. Furthermore, several cost analysis studies have demonstrated that spinal cord stimulation is cost effective for these approved conditions. Despite the lack of a comprehensive mechanism, the technology and the complexity in which spinal cord stimulation is being utilized is growing. Newer devices are targeting axial low back pain and foot pain, areas that have been reported to be more difficult to treat with traditional spinal cord stimulation. Percutaneous hybrid paddle leads, peripheral nerve field stimulation, nerve root stimulation, dorsal root ganglion, and high frequency stimulation are actively being refined to address axial low back pain and foot pain. High frequency stimulation is unique in that it provides paresthesia free analgesia by stimulating beyond the physiologic frequency range. The preliminary results have been mixed and a large randomized control trial is underway to evaluate the future of this technology. Other emerging technologies, including dorsal root ganglion stimulation and hybrid leads, also show some promising preliminary results in non-randomized observational trials. Limitation: This review is a primer and not an exhaustive review for the current evidence supporting the use of spinal cord stimulation and precursory discussion of emerging neuromodulation technologies. This review does not address peripheral nerve stimulation and focuses mainly on spinal cord stimulation and touches on peripheral nerve field stimulation. Conclusions: Spinal cord stimulation has demonstrated clinical efficacy in randomized control trials for the approved indications. In addition, several open label observational studies on peripheral nerve field stimulation, hybrid leads, dorsal root ganglion stimulation, and high frequency stimulation show some promising results. However, large randomized control trials demonstrating clear clinical benefit are needed to gain evidence based support for their use. Key words: Spinal cord stimulation, chronic pain; low back pain, high frequency stimulation, peripheral nerve field stimulation, dorsal root ganglion stimulation, failed back surgery syndrome, complex regional pain syndrome, critical limb ischemia, refractory angina pectoris

Background: Postherpetic neuralgia (PHN) is the most common complication of shingles and can be a significant burden to patients due to pain and disability. Currently, treatment options are limited. In refractory cases, neuromodulation using spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) have been used but is considered experimental due to limited evidence. Case Report: We report 2 cases who experienced successful treatment of refractory PHN. Patients underwent dorsal root ganglion (DRG) stimulation at the thoracic level for the treatment of refractory PHN. Conclusion: Both patients showed significant improvement in pain at 24 and 36 months after a DRG stimulation trial and implantation. We report the successful use of DRG stimulation for the treatment of PHN. Key words: Knee, genicular, radiofrequency ablation, osteoarthritis, pain, block, cooled

BACKGROUND: The treatment of complex regional pain syndrome (CRPS) is a difficult endeavor. The advent of neuromodulation interventions has led to new therapeutic options for chronic pain syndromes. Coinciding neuromodulation devices, such as spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRGS), may have a part in refractory CRPS. CASE REPORT: The authors present a case of a 50-year-old man status post a traumatic skiing accident 3 years prior to presentation with residual CRPS symptoms after an SCS implant. Additional multilevel coverage for refractory chronic neuropathic pain was achieved with the implantation of multiple DRGS devices. DISCUSSION: This case provides support for the use of DRGS in patients needing supplementary neuropathic pain coverage. Outcomes were reflected in diminished pain scores, an enriched quality of life, and enhanced functional capacity measures. KEY WORDS: Complex regional pain syndrome, dorsal root ganglion stimulator, dorsal root ganglion stimulation, neuromodulation, spinal cord stimulator, spinal cord stimulation, chronic pain, case report

Complex regional pain syndrome (CRPS) is a chronic debilitating multisystem neuropathic pain disorder. It is characterized by continuous pain, usually out of proportion to any known tissue injury, vasomotor changes, sudomotor or edema, and motor or trophic changes. The objective of this study is to assess the efficacy of neuromodulation, interventional, and unconventional treatments for CRPS. The primary focus is pain reduction, assessed through various scales, with secondary outcomes examining effects on autonomic, sensory, motor, and psychological aspects, and quality of life. PubMed, Cochrane Library, MDPI, and ScienceDirect databases were thoroughly searched using our detailed search strategy and relevant literature compiled. Articles were assessed using our eligibility criteria and quality appraisal tools. All types of study designs were considered. Initially, 463 articles were identified; after a thorough assessment, 23 articles comprising 2307 patients were shortlisted. Neuromodulation interventions, specifically Dorsal Root Ganglion (DRG) and Spinal Cord Stimulation (SCS) demonstrated statistically significant pain reduction (43-82% and up to 70%, respectively). Both modalities demonstrate improvement in secondary outcomes and quality of life. Interventional interventions, specifically nerve blockade ranging from sympathetic, stellate ganglion, and regional nerve blocks, all demonstrate varying levels of efficacy on measured pain and secondary outcomes. Unconventional: Botulinum toxin injections through multiple delivery systems demonstrated varying levels of efficacy in treating pain and improving secondary outcomes. In conclusion, DRG stimulation and SCS, nerve blockade, and botulinum toxin all display promise in alleviating symptoms of CRPS. Definite conclusions were not made due to a lack of clinical trial data, and longer multi-year follow-up is recommended.

ID: 217375 Dorsal Root Ganglion Stimulation: An Off-Label Indication for Targeted Coverage of Chronic Pelvic Pain

Dorsal root ganglion (DRG) stimulation is a novel neuromodulation approach to treat the chronic pain of complex regional pain syndrome (CRPS) in the lower extremity. DRG stimulation targets specific dorsal root ganglia, which are located near the spinal cord and are the key relay centers responsible for transmitting sensory signals from peripheral to the central nervous system. DRG stimulation modulates these pain sensory pathways by selectively stimulating the DRG associated with the affected limb or body region. It modulates sensory neurons and reduces the pain signals that transmit to the central nervous system. DRG stimulation provides a higher percentage of response and less paresthesia compared to the traditional spinal cord stimulation in patients with CRPS.

Context: Pudendal neuralgia is a chronic neuropathic pain syndrome worsening throughout daily activities. Although temporarily relieved when standing or lying down, it is often misdiagnosed, improperly treated, and/or refractory to treatment leading to a negative impact on quality of life. The lack of research in proper diagnosis and interventional management (such as dorsal root ganglion stimulation (DRGS) and pudendal nerve block) further contributes to the delay in relief from the chronic pain. Objective: The goal of this scoping review is to assess if research exists on benefits and risks of pudendal nerve block and dorsal root ganglion and their effectiveness both individually and in comparison to each other in the management of pudendal neuralgia. Methods: An organized review of current literature evaluated the benefits of pudendal nerve block and dorsal root ganglion in treatment of pudendal neuralgia. The search was performed using the database Pubmed. The following search terms were utilized: “pudendal neuralgia”, “pudendal neuralgia dorsal root ganglion stimulation”, “pudendal neuralgia and pudendal nerve block”, “pudendal neuralgia and pudendal nerve block benefits”, “pudendal neuralgia treatment”. Systemic reviews, case reports, clinical trials, and review trials were included in our analysis. Articles that did not focus on either pudendal neuralgia or the use of pudendal nerve blocks or DRGS were excluded. Results: There were limited studies that focused on the use of DRGS for pudendal neuralgia compared to pudendal nerve blocks. Conclusion: Though the benefits and disadvantages of each treatment were assessed in the studies, there is no research directly comparing the two treatment options leading to lack of current recommendations or guidelines based on treatment efficacies. Future directions: Further research needs to be conducted on use of DRGS as well as a comparison study to acknowledge its effectiveness compared to pudendal nerve blocks.

ID: 203617 One-Year Safety Analysis Using DRG-Stimulation for the Treatment of Lower Limbs CRPS I and II

Selective intradural dorsal rhizotomy for persistent radicular leg pain: a contemporary series

ABSTRACTIntroduction: Spinal cord stimulation has emerged as a state-of-the-art evidence-based treatment for chronic neuropathic pain and mixed nociceptive–neuropathic pain. In recent years, several newer devices and treatment algorithms have provided unique and effective ways of treating chronic pain by spinal cord stimulation. In a previous review, the authors commented on the 5-year forecast for high frequency and Burst waveforms, as the only two paresthesia independent SCS strategies. Over the last 5 years, there has been considerable addition to the outcome data related to these modalities. Additionally, new treatment algorithms and modalities for spinal cord stimulation have emerged. In this review, the authors provide an up to date summary of these modalities of treatment, indications, and evidence on all different modalities and programming paradigms that are available today.Areas covered: A literature review was performed using key bibliographic databases to find outcomes related studies pertaining to spinal cord stimulation, limited to the English language and human data, between 2010 and 2018. The literature search yielded the following based on our inclusion criteria; six articles on burst stimulation, three articled on high density/high dose stimulation, six articles on Dorsal Root Ganglion stimulation, nine articles on high-frequency stimulation, and one article on closed-loop stimulation. We have also included in the discussion some smaller and anecdotal studies.Expert commentary: The evidence to support outcomes of spinal cord stimulation has evolved considerably since our last review in 2014. New targets, frequencies and pulse trains, and feedback appear to have advanced the efficacy of spinal cord stimulation. Future developments aim to continue to refine patient selection and maintenance of patients in therapy.

ID: 205005 Dorsal Root Ganglion Stimulation at L1 & L2 for Post- Ilioinguinal, Iliohypogastric, and Genitofemoral Neurectomy

In recent years, neuromodulation has experienced a renaissance. Novel waveforms and anatomic targets show potential improvements in therapy that may signify substantial benefits. New innovations in peripheral nerve stimulation and dorsal root ganglion stimulation have shown prospective evidence and sustainability of results. Sub-perception physiologic bursting, high-frequency stimulation and feedback loop mechanisms provide significant benefits over traditional tonic spinal cords stimulation (SCS) in peer reviewed investigations. We reviewed the themes associated with novel technology in the context of historical stalwart publications. New innovations have led to better nerve targeting, improvements in disease-based treatment, and opioid alternatives for those in chronic pain. In addition, new neural targets from both structural and cellular perspectives have changed the field of Neurostimulation. For many years, tonic SCS was representative of neuromodulation, but as this review examines, the progression of the field in the past decade has reshaped patient options.

Spinal cord and dorsal root ganglion stimulation are minimally invasive surgical techniques used to treat an array of chronic pain disorders. There is a paucity of data related to defining best practices in these specific patient populations, and historically, providers have relied on consensus committees to opine on the best techniques for patient safety and experience. The most efficacious mechanism of surgical closure—specifically a running suture closure compared to a surgical staple closure—is debated. A retrospective review of 155 patients implanted with either a spinal cord or dorsal root ganglion stimulator between 2017 and 2019 was undertaken to determine if the type of surgical closure was related to degree of postoperative surgical site discomfort. The primary outcome showed no statistically significant difference on postoperative pain scores between the suture (6.0 (IQR 5.0–8.0)) and staple (7.0 (IQR 5.0–8.0)) cohorts at postoperative day (POD) #1 (adjusted β 0.17 (95% CI −0.61 to 0.95), P=0.670). This finding held for postoperative pain scores at POD #10 as well (staples (1.0 (IQR 0.0–4.0)) and suture (2.0 (IQR 0.0–5.0), adjusted β −0.39 (95% CI −1.35 to 0.58), P=0.432)). A regression analysis was performed to identify secondary factors impacting postoperative pain scores. Higher preoperative pain score (β 0.50 (95% CI 0.09 to 0.92), P=0.019) and female gender (β 1.09 (95% CI 0.15 to 2.02), P=0.023) were predictive of higher incisional pain scores at POD#10. Increasing age was associated with decreased incisional pain scores at POD#10 (β −0.06 (95% CI −0.09 to −0.03), P < 0.001). These findings are of interest to the pain practitioner and may be valuable in preoperative discussions with prospective patients.

Dorsal Root Ganglion Stimulation as a Salvage Therapy Following Failed Spinal Cord Stimulation