Very Low Frequencies Maintain Pain Relief From Dorsal Root Ganglion Stimulation: An Evaluation of Dorsal Root Ganglion Neurostimulation Frequency Tapering

BackgroundDorsal root ganglion neurostimulation (DRG-S) is effective in treating various refractory chronic pain syndromes. In preclinical studies, DRG-S at very low frequencies (<5 Hz) reduces excitatory output in the superficial dorsal horn. Clinically, we have also observed the effectiveness of DRG-S at low frequencies. We conducted a case series to describe the effect of very low-frequency DRG-S stimulation on clinical outcomes.Materials and MethodsDRG-S for refractory low back pain was initiated at parameters consistent with published values. Thereafter, the stimulation frequency of DRG-S was reduced in a stepwise fashion to the lowest frequency that maintained pain relief. Pain intensity, disability, and general health status data were collected at baseline, prior to initiation of tapering, and at four weeks after each patient’s lowest effective stimulation frequency was reached.ResultsAfter device activation (N = 20), DRG-S frequency was tapered from 16 to 4 Hz over a 4- to 17-week period, reducing charge-per-second by nearly two-thirds. Even so, pain relief was maintained at more than 75%, with consistent findings in the other measures.ConclusionDRG-S may have utility in treating chronic pain at lower stimulation frequencies than previously recognized. We have previously theorized that the mechanism of action may involve preferential recruitment of low-threshold mechanoreceptor fibers via the endogenous opioid system. Of clinical relevance, lower frequency stimulation maintains DRG-S efficacy regarding improvements in pain, disability, and quality of life. It can extend battery life and may potentially lead to the development of smaller implantable pulse generators.     

Prospective Observational Cohort Study on Dorsal Root Ganglion Stimulation in Chronic Postsurgical Pain: Results of Patient-Reported Outcomes at Two Years

ObjectivesThis study aimed to determine the long-term effects of dorsal root ganglion (DRG) stimulation on pain, physical function, and quality of life in patients with chronic postsurgical pain. We hypothesized that the effects of DRG stimulation would be sustainable through two years of follow-up.Materials and MethodsThis prospective observational cohort will include 30 patients, at least 18 years old, scheduled to receive DRG stimulation in two Dutch hospitals. A minimum pain score of 50 mm on a 100-mm visual analog scale was required. Following written informed consent, patients completed validated questionnaires on pain, physical function, and quality of life at baseline, one year, and two years. Change over time was analyzed using mixed model statistics, with Tukey-Kramer correction. A p-value of <0.05 was considered statistically significant.ResultsFollow-up was completed by 22 of 30 enrolled patients. Pain scores decreased at one year (?38 ± 7, 95% CI [?51 to ?25], p < 0.001) and two years (?29 ± 6, 95% CI [?42 to ?17], p < 0.001) compared with those at baseline. Physical function measured with pain severity and interference decreased at one and two years (?2.5 ± 0.5, 95% CI [?3.3 to ?1.5], p < 0.001, and ?2.3 ± 0.5, 95% CI [?3.3 to ?1.3], p < 0.001, respectively). Quality of life increased over time (0.22 ± 0.05, 95% CI [11–33], p < 0.001, at one year; 0.21 ± 0.05, 95% CI [10–31], p = 0.001, at two years).ConclusionsDRG stimulation in chronic postsurgical pain is associated with a sustainable reduction in pain and an improvement in physical function and in quality of life, through two years of follow-up.     

Complications and Effects of Dorsal Root Ganglion Stimulation in the Treatment of Chronic Neuropathic Pain: A Nationwide Cohort Study in Denmark

ObjectivesDorsal root ganglion (DRG) stimulation is a novel treatment of chronic neuropathic pain and has been shown to be efficacious across several case reports and randomized trials. However, long-term follow-up is limited, as are reports of complication rates. This study presents efficacy and complications for patients treated with DRG stimulation.Materials and MethodsWe performed an observational, multicenter cohort study of all patients in Denmark implanted with FDA-approved DRG stimulation systems to treat chronic, neuropathic pain between 2014 and 2018. Follow-up period was one to three years.ResultsForty-three patients underwent trial DRG stimulation; 33 were subsequently fully implanted. Pain location: 58% lower extremity; 21% upper extremity; 21% thoracic/abdominal. At the end of the observation period, 58% of fully implanted patients were still implanted; 42% had fully functional systems.In these patients, average Numerical Rating Scale (NRS)-score of pain was reduced from 6.8 to 3.5 (p = 0.00049) and worst NRS-score was reduced from 8.6 to 6.0 (p = 0.0039) at 12 months follow-up. Pain Catastrophizing Score was reduced from 32 to 15 (p = 0.0039).Thirteen patients experienced complications related to defect leads (39% of implanted systems). In four patients (12%), lead removal left fragments in the root canal due to lead fracture, and three patients suffered permanent nerve damage during attempts to replace broken leads.ConclusionsThis study suggests a significant, clinically relevant effect of DRG stimulation on neuropathic pain, but also demonstrates substantial problems with maintenance and revision of currently available systems. Consequently, treatment with equipment marketed specifically for DRG stimulation is currently paused in Denmark.     

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis

ObjectiveSpinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study.Materials and MethodsThe EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits.ResultsThe mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved “good sleep quality” scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. “Normative” sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months.ConclusionsECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology.Clinical Trail RegistrationThe Clinicaltrials.gov registration number for the study is NCT02924129.