Dorsal Root Ganglion Stimulation Research Articles

Chronic pelvic pain and role of dorsal root ganglion stimulation.

Chronic pelvic pain and role of dorsal root ganglion stimulation.

4. Painful diabetic polyneuropathy.

Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek medical attention. The number of people suffering from painful diabetic polyneuropathy (PDPN) has increased significantly over the past decades. The literature on the diagnosis and treatment of diabetic polyneuropathy was retrieved and summarized. The etiology of PDPN is complex, with primary damage to peripheral nociceptors and altered spinal and supra-spinal modulation. To achieve better patient outcomes, the mode of diagnosis and treatment of PDPN evolves toward more precise pain-phenotyping and genotyping based on patient-specific characteristics, new diagnostic tools, and prior response to pharmacological treatments. According to the Toronto Diabetic Neuropathy Expert Group, a presumptive diagnosis of "probable PDPN" is sufficient to initiate treatment. Proper control of plasma glucose levels, and prevention of risk factors are essential in the treatment of PDPN. Mechanism-based pharmacological treatment should be initiated as early as possible. If symptomatic pharmacologic treatment fails, spinal cord stimulation (SCS) should be considered. In isolated cases, where symptomatic pharmacologic treatment and SCS are unsuccessful or cannot be used, sympathetic lumbar chain neurolysis and/or radiofrequency ablation (SLCN/SLCRF), dorsal root ganglion stimulation (DRGs) or posterior tibial nerve stimulation (PTNS) may be considered. However, it is recommended that these treatments be applied only in a study setting in a center of expertise. The diagnosis of PDPN evolves toward pheno-and genotyping and treatment should be mechanism-based.

Chemotherapy-induced peripheral neuropathy: Role of dorsal root ganglion stimulation.

Chemotherapy-induced peripheral neuropathy: Role of dorsal root ganglion stimulation.

Prediction of cell-cell communication patterns of dorsal root ganglion cells: single-cell RNA sequencing data analysis.

Abstract JOURNAL/nrgr/04.03/01300535-202406000-00042/inline-graphic1/v/2023-10-30T152229Z/r/image-tiff Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system, and dorsal root ganglion neuron excitability affects pain perception. Dorsal root ganglion stimulation is a new approach for managing pain sensation. Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies. Here, we used the single-cell RNA-sequencing (scRNA-seq) database to investigate intercellular communication networks among dorsal root ganglion cells. We collected scRNA-seq data from six samples from three studies, yielding data on a total of 17,766 cells. Based on genetic profiles, we identified satellite glial cells, Schwann cells, neurons, vascular endothelial cells, immune cells, fibroblasts, and vascular smooth muscle cells. Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive, itch, touch, mechanical, heat, and cold sensations. Moreover, we predicted several distinct forms of intercellular communication among dorsal root ganglion cells, including cell-cell contact, secreted signals, extracellular matrix, and neurotransmitter-mediated signals. The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b (A2B) receptor and glial cell line-derived neurotrophic factor family receptor alpha 1 (GFRα-1). Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1. Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner. Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation. Furthermore, our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms. Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

Peripheral nerve stimulation for the treatment of chronic knee pain

The average age of our population is increasing, resulting in a high incidence of chronic degenerative knee pathologies. Several treatment options, including surgical procedures are available to help mitigate these pathologies. However, the percentage of subjects with chronic post-surgical knee pain is still estimated at 16–20%. Neuromodulation techniques such as spinal cord stimulation and dorsal root ganglion stimulation (DRGS) are treatment options for subjects with chronic knee pain. The evidence for peripheral nerve stimulation (PNS) is minimal due to a limited number of neuromodulation systems capable of targeting the distal part of the lower limbs. This study aimed to investigate the safety and efficacy externally powered PNS systems for the treatment of chronic intractable knee pain targeting the saphenous nerve. Patients suffering from chronic intractable post-surgical knee pain received landmark-guided peripheral nerve stimulation of the branches of the saphenous nerve. All implants were performed with an externally powered PNS system to avoid lead migration as a result of cross-joint lead positions tunneling towards an Implantable Pulse Generator to the trunk. Data were collected retrospectively. Subject-reported outcome was measured via numerical rating scale values on a 10-point scale measuring pain intensity at rest and in motion. Additional data were collected for the subjects treated at the Charité location, including quality of life with the SF-36 form, quality of sleep with the Pittsburgh Sleep Quality Index and mood states with the short form of the General Depression Scale. Thirty-three patients received direct to permanent implant, landmark-guided peripheral nerve stimulation of the saphenous nerve branches. Six (18.2%) subjects reported non-sufficient initial benefit from the therapy and were explanted. Two subjects were explanted due to wound infections. The total study population reported included 25 patients. These subjects reported significant improvements related to pain, quality of life, mood quality, and quality of sleep. Additionally, subjects were able to reduce their opioid medication significantly after PNS therapy. Externally powered PNS at the saphenous nerve branches is a straightforward, selective and safe technique for patients with chronic knee pain. The landmark-guided implantation technique is less invasive than classical neuromodulation techniques such as spinal cord or DRGS and complication rates remain low. Short-term results are promising and show considerable reductions in pain scores and opioid intake. Long-term results are pending.

Current Neurostimulation Therapies for Chronic Pain Conditions.

Neurostimulation treatment options have become more commonly used for chronic pain conditions refractory to these options. In this review, we characterize current neurostimulation therapies for chronic pain conditions and provide an analysis of their effectiveness and clinical adoption. This manuscript will inform clinicians of treatment options for chronic pain. Non-invasive neurostimulation includes transcranial direct current stimulation and repetitive transcranial magnetic stimulation, while more invasive options include spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), dorsal root ganglion stimulation, motor cortex stimulation, and deep brain stimulation. Developments in transcranial direct current stimulation, repetitive transcranial magnetic stimulation, spinal cord stimulation, and peripheral nerve stimulation render these modalities most promising for the alleviating chronic pain. Neurostimulation for chronic pain involves non-invasive and invasive modalities with varying efficacy. Well-designed randomized controlled trials are required to delineate the outcomes of neurostimulatory modalities more precisely.

Scrambler Therapy for Patients With Complex Regional Pain Syndrome: A Case Series.

Complex regional pain syndrome is a chronic debilitating pain disorder that is difficult to manage, in part due to its heterogeneous clinical presentation and lack of clearly defined pathophysiology. Patients usually require a multidisciplinary approach to treatment, which can entail pharmacotherapy, physical therapy, behavioral therapy, and interventional pain procedures, such as sympathetic nerve blocks, spinal cord stimulation, and dorsal root ganglion stimulation. However, many patients continue to experience pain refractory to these multimodal strategies. Scrambler therapy (ST) is a noninvasive method of neuromodulation that is applied through cutaneous electrodes, and can alleviate chronic neuropathic pain by stimulating C-fibers and replacing endogenous pain signals with synthetic non-nociceptive signals. Although the use of ST has been reported for several types of refractory central and peripheral neuropathic pain, there is a paucity of data regarding the use of ST for complex regional pain syndrome. We present two patients with complex regional pain syndrome of the right lower extremity, who each underwent ST and experienced significant pain relief and improvement in function and quality of life.

Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation: A Proposal for Standardization in Fellowship and Training Programs.

The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation.

Lead migration rate in dorsal root ganglion stimulation using lead anchoring techniques: A follow-up study.

Lead anchoring has previously been shown to reduce the rate of dorsal root ganglion stimulation (DRG-S) lead migration. The aim of this study was to assess longer-term follow-up and consistency of lead migration prevention with lead anchoring in a new cohort of patients. We performed a retrospective chart review from September 2017 to November 2022 of all patients who had DRG-S implants at our institute to identify the number of lead migrations that occurred over this period. The first cohort consisted of patients reported on in a previous publication (implanted from September 2017 through September 2020) subdivided into unanchored or anchored lead groups. The second cohort consisted of patients implanted during or after October 2020 who were not previously reported on for whom leads were anchored using silastic anchoring only. At the November 2022 data cutoff, in the initial cohort, 8 migrations had occurred in unanchored leads over an average follow-up of 49 months, equating to a migration rate of 9.1% per lead. Patients with anchored leads in the initial cohort experienced 2 migrations over an average follow-up of 38 months (0.7% migration rate per lead). There were no new lead migrations in these groups over the extended follow-up reported here. The migration rate in the new cohort was similar, with 1 migration over an average follow-up of 13 months (0.5% migration rate per lead). These results underscore the necessity of anchor placement during DRG-S lead implantation to prevent lead migration.

Bilateral T12 Dorsal Root Ganglion Stimulation for the Treatment of Low Back Pain With 20-Hz and 4-Hz Stimulation, a Retrospective Study

ObjectivesChronic low back pain (CLBP) is one of the most common chronic pain conditions that cause both individual suffering and a burden to society. For these patients, several interventional treatment options such as surgery, blocks, radiofrequency, and spinal cord stimulation are available. Lately, dorsal root ganglion stimulation (DRG-S) also has been mentioned as an option by targeting bilateral T12 dorsal ganglia. In this study, we present the outcome of 11 patients with CLBP treated with bilateral T12 DRG-S. Materials and MethodsThirteen patients with CLBP with and without leg pain were treated with bilateral T12 DRG-S. Three of the patients also received a third lumbar lead owing to leg pain. Eleven of the patients had >50% pain relief during the peri- or/and postoperative testing and received a fully implantable neurostimulator. Pain intensity, general health status, quality of life, pain catastrophizing, mental status, sleeping disorder, physical activity, and patient satisfaction were followed using numeric rating scale (NRS), Patient-Reported Outcomes Measurement Information System 29 version 2.1, Pain Catastrophizing Score, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire Depression Module, Insomnia Severity Index, and Patient Satisfaction Questionnaire at baseline before implantation and at three months and six months. The results were analyzed on the basis of six domains: pain relief, sleeping disorder, social ability, mental status, physical activity, and satisfaction. To be identified as a responder, the patients should show a significant improvement in the pain relief domain together with at least two other domains. All responders also were given the opportunity to test 4-Hz DRG-S and compare it with traditional 20-Hz stimulation. ResultsAll 11 patients were identified as responders at six months. Five of the patients had >80% pain relief, with an average NRS score reduction of 71% for the whole group. Significant improvement could be observed in three domains for one patient, four domains for three patients, five domains for six patients, and six domains for one patient. Seven patients chose to try 4-Hz stimulation. All seven identified 4-Hz stimulation as at least as good as or better than 20-Hz stimulation and chose to continue with 4-Hz stimulation. ConclusionsBilateral T12 DRG-S seems to be an effective treatment for chronic low back pain, with significant beneficial effect not only on pain but also on quality of life, pain catastrophizing, mental status, sleeping disorder, and physical activity. 4-Hz DRG-S gave a result comparable with or better than 20-Hz stimulation.

Exploring Psychophysical and Neurophysiological Responses to Intra-Epidermal Electrical Stimuli in Patients With Persistent Spinal Pain Syndrome Type 2 with a Spinal Cord Stimulator.

There is a lack of measures that provide insights into how spinal cord stimulation (SCS) modulates nociceptive function in patients with persistent spinal pain syndrome type 2 (PSPS-T2). Recently, we observed altered nociceptive detection thresholds (NDTs) in response to intra-epidermal electrical stimulation (IES) on the feet of PSPS-T2 patients when dorsal root ganglion stimulation was turned on. Furthermore, we observed altered NDTs and evoked potentials (EPs) in response to IES on the hands of PSPS-T2 patients. To explore whether EPs were obstructed by SCS artifacts, we applied IES twice to the hands of patients with SCS turned on (SCS-ON/ON group). To explore possible confounding effects of SCS outside the stimulated area, we repeated IES on the hands of these patients, once with SCS turned off and subsequently once with SCS turned on (SCS-OFF/ON group). The results demonstrated that EPs were not obstructed by SCS artifacts. Additionally, NDTs and EPs did not significantly change between measurements in the SCS-ON/ON and the SCS-OFF/ON groups. Therefore, the results suggested that possible confounding effects of SCS outside the nociceptive system did not interfere with the detection task performance. This work warrants further exploration of NDT-EP phenomena in response to IES at the painful feet of patients.Clinical Relevance-This work contributes to developing a clinical tool to explore psychophysical and neurophysiological biomarkers for observing modulating effects of SCS in patients with PSPS-T2.

Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation of C2 Dorsal Root Ganglion for the Treatment of Refractory Atypical Facial Pain: A Technical Report and Case Series

BackgroundChronic craniofacial pain can be difficult to manage clinically. This technical report documents the peripheral nerve stimulation of the C2 dorsal root ganglion as an effective modality to treat refractory atypical facial pain. Materials and MethodsIn this case series, three patients with chronic refractory atypical facial pain and p >50% pain relief following diagnostic C2 dorsal root ganglion blockade underwent ultrasound-guided percutaneous placement of a peripheral nerve stimulator adjacent to the C2 dorsal root ganglion. Patients were then observed clinically and monitored for improvement in symptoms and adverse events. ResultsThree patients underwent peripheral nerve stimulator placement. At follow-up, there were no reported adverse events, and all patients reported satisfactory improvement in pain. ConclusionThe neuromodulation of C2 dorsal root ganglion via ultrasound-guided percutaneously implanted peripheral nerve stimulator is a novel and potentially effective approach for the management of chronic refractory craniofacial pain.

ID: 212641 Salvage Therapy With Bilateral T12 and S1 DRG Stimulation for Post-Laminectomy Syndrome: A Case Report

Neuromodulation with tonic spinal cord stimulation (t-SCS) is well evidenced to manage chronic pain syndromes. However, for patients with post-laminectomy syndrome refractory to t-SCS, salvage therapies such as alternative waveforms of SCS (burst, high frequency, or multiple waveform) or dorsal root ganglion (DRG) stimulation have been studied. DRG stimulation is an emerging option for salvage therapy and was shown to be non-inferior and superior to t-SCS in treating lower extremity neuropathic pain for CRPS in the ACCURATE study. DRG stimulation’s use as salvage therapy for post-laminectomy syndrome is poorly reported. In this case, we present the treatment approach with DRG stimulation as salvage treatment for post-laminectomy syndrome refractory to t-SCS.

ID: 209955 Dorsal Root Ganglion Stimulation as an Effective Modality for Pelvic Pain From Rectal Cancer

Cancer related pelvic pain severely impairs the quality of life and can be resistant to a variety of interventions. Neuromodulation is emerging as a potential avenue to manage pain and improve quality of life. Unlike Spinal cord stimulators (SCS), dorsal root ganglion (DRG) stimulation targets focal areas and is an attractive target for neurostimulation. Over the past decade, DRG stimulation has become a part of the armamentarium to effectively treat discrete areas of pain particularly resistant to other interventional modalities. A case series showed significant analgesic benefit from DRG stimulation with L1/S2 lead placement in patients with chronic pelvic pain resistant to a variety of other therapies.

ID: 200814 Open Dorsal Root Ganglion Stimulator Lead Placement in the Setting of Previous Fusion: Case Report

Dorsal Root Ganglion (DRG) Stimulation is a relatively new neuromodulation technique that has been showing increasing promise in chronic pain management. Due to unique anatomical attributes, DRG stimulation allows for posture independent, precise, and targeted neuromodulation with lower energy use, leading to the need for fewer generator changes.

Dorsal root ganglion stimulation for chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common consequence of cancer treatment that can be persistent and difficult to manage. Dorsal root ganglion stimulation (DRG-S) is a recently introduced but understudied treatment modality. This study explored the effect of DRG-S on pain and symptom burden associated with CIPN. Patients with CIPN who underwent a DRG-S trial between January 2017 and August 2022 were identified through chart review after IRB approval was obtained. Demographic data, procedure details, pre-and postoperative scores, including the Numerical Rating Scale (NRS) and Edmonton Symptom Assessment System (ESAS), and duration of follow-up were recorded. Statistical analysis included descriptive statistics and paired t-tests to compare pre-and postoperative scores. Nine patients with an even mix of solid and hematologic malignancies underwent DRG-S trial and had a statistically significant decrease in NRS scores, with a mean reduction of 2.3 in their average pain (p = 0.014), 2.6 in worst pain (p = 0.023), and 2.1 in least pain (p = 0.018). Eight patients (88.9%) underwent permanent DRG-S implantation. Mean NRS scores remained lower than preoperative baselines through the first year of follow-up. Statistically significant reductions were noted at 3 months in average (2.1, p = 0.006) and least pain scores (1.9, p = 0.045), which further decreased after 6-12 months (average: 3.6, p = 0.049; least: 3.4, p = 0.023). Only the pain component of ESAS scores showed a significant reduction with DRG-S (2.0, p = 0.021). All patients endorsed improved sensation, 75% decreased their pain medication usage, and 37.5% reported complete pain relief by 2 years. Dorsal root ganglion stimulation can be an effective treatment for pain related to CIPN and deserves further investigation.

ID: 211385 Modeling the Effects of Dorsal Root Ganglion Stimulation on a Population of Biophysically Distinct C-neurons

Dorsal root ganglion stimulation (DRGS) is an effective therapy for managing chronic pain. However, some patients do not receive adequate pain relief from DRGS. We do not understand the mechanisms of action of DRGS-induced pain relief, preventing us from optimizing the therapy to maximize pain relief in all patients. One hypothesis is that DRGS augments the filtering of action potentials (APs) at the T-junction of nociceptive C-neurons. However, conventional neurostimulation theory suggests direct action on nonmyelinated cells, such as C-neurons, is unlikely at stimulation amplitudes utilized in clinical DRGS programming. We employed a computational approach to study how biological variability between C-neurons may affect their response to DRGS.

ID: 210523 Prospective Evaluation of Washout Periods Following Dorsal Root Ganglion Stimulation Trial

Dorsal root ganglion stimulation (DRG-S) places an electrical field over the DRG to modulate neural transmission. As mechanisms underlying DRG-S have become elucidated, it is clear there are actions distinct from that of conventional spinal cord stimulation (SCS). DRG-S is efficacious when delivered as a subthreshold and paresthesia-free tonic waveform, at frequencies as low as 4 Hz, and when stimulation is delivered intermittently, none of which are possible with SCS. The endogenous opioid system may play a role in pain relief with DRG-S, which should lead to prolonged washout times based on preclinical research. This study aimed to measure the time for pain to return to baseline pain levels after subjects’ 1-week DRG-S trials ended.

ID: 210704 Objectively Measured Improvement in Patients Treated With Dorsal Root Ganglion Stimulation

Dorsal root ganglion stimulation (DRG-S) is effective in treating CRPS type I or II (causalgia) of the groin and lower extremities. Despite considerable efforts toward establishing biomarkers of pain, methods to measure pain are primarily focused on patient reported outcomes (PRO). This study will quantify changes in function, affect, sleep, and quality of life using a commercially available wearable device and correlate these objective metrics with patient-reported outcomes collected prior to and post permanent implant of a DRG-S system.

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

Dorsal root ganglion stimulation (DRG-S) is effective for the treatment of chronic focal pain conditions1 and superior to traditional spinal cord stimulation (SCS) in the treatment of CRPS types I and II (causalgia).2,3 To provide continued evidence of safety after FDA approval, a post-market, prospective, single-arm, observational study in patients with CRPS types I or II of the lower limbs treated with DRG-S was designed (NCT02800863). The primary goal of the study was to show that the proportion of serious adverse effects (SAEs) in subjects who received a permanent implant was lower than a pre-specified goal of 15.5% after 12 months. SAEs were defined as safety-related device and non-device events that result in the subject's death or a serious deterioration in health that is life-threatening, results in permanent impairment, or requires medical intervention and hospitalization. The study descriptive endpoint was the proportion of subjects with device, procedure, or stimulation-related SAEs (SADE) or AE (ADE)