Dorsal Root Ganglion Stimulation for the Management of Inflammatory Bowel Disease: A Case Report.

This case report presents the successful use of dorsal root ganglion stimulation (DRGS) in a 30-year-old female patient with Crohn's disease. Despite extensive treatments, the patient experienced chronic abdominal pain, diarrhea, bloating, cramping, fatigue, and other debilitating symptoms. After a successful DRGS trial with leads placed on the right T6 and T10, she was implanted with a permanent system. At 18 months she continues to experience significant improvement in symptoms, including reduced abdominal pain, decreased defecation frequency, better stool consistency, less pain with eating and bowel evacuation, and enhanced quality of life.

Evaluation of Washout Periods After Dorsal Root Ganglion Stimulation Trial.

OBJECTIVE: Dorsal root ganglion stimulation (DRG-S) is a novel therapy to treat chronic pain. It has shown efficacy when delivered intermittently, suggesting a delayed washout effect exists. To measure the washout period, and to determine whether there are differences in washout times among different types of treated pain, we measured the time for pain to return at the end of the patients' one-week DRG stimulation trials. MATERIALS AND METHODS: Patients who completed a successful DRG-S trial were included. The times until 25% (t25) and 90% (t90) of baseline pain level returned were recorded. The patients were divided into neuropathic, nociceptive, and mixed pain groups for subgroup comparison. t25 and t90 were plotted in the entire cohort and subgroups using reverse Kaplan-Meier plots (failure curves) and compared using a log-rank test. RESULTS: In total, 29 consecutive patients were included. Median t25 and t90 times were 7.1 and 19.5 hours, respectively. Median (interquartile range) times were longest for the nociceptive pain group (n = 17) and shortest for the neuropathic pain group (n = 6), with the mixed-pain group (n = 6) in between (t25: 7.1 [1.7-19.4], 3.40 [1.4-8.4], and 5.7 [0.8-17.6]; t90, 22.0 [10.7-71.0], 7.6 [3.6-19.8], and 20.9 [14.2-31.2], respectively). t90 times differed significantly by pain type (p = 0.040). CONCLUSIONS: This study showed a prolonged washout period after cessation of DRG-S therapy. Washout times vary according to pain type. The observed effects are possibly due to long-term depression of pain signaling and could allow the implementation of alternative stimulation strategies with DRG-S. Further investigations evaluating DRG-S washout times are warranted.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: These results underscore the necessity of anchor placement during DRG-S lead implantation to prevent lead migration.

Dorsal Root Ganglion Stimulation to Treat Chronic Shoulder Pain: A Case Report.

A 67-year-old man presented with severe 9 of 10 intractable pain of the left shoulder joint after arthroplasty and revision surgeries, with associated weakness, atrophy, and limited range of motion in all directions. Dorsal root ganglion stimulation (DRG-S) at the left C4, C5, and C6 levels was used after failed conservative and interventional measures, resulting in significant improvement in pain, function, and quality of life measures through 6 months postimplantation. Larger studies should examine if DRG-S is effective in treating chronic arthritic joint pain as well as chronic postsurgical pain of the shoulder that is not predominantly neuropathic.

Dorsal root ganglion stimulation for the treatment of joint pain with predominantly nociceptive characteristics: A case series.

INTRODUCTION: Dorsal root ganglion stimulation (DRG-S) has recently emerged as a novel therapy in neuromodulation that demonstrated a higher rate of success than spinal cord stimulation (SCS) in a prospective, head-to-head randomized comparative trial to treat complex regional pain syndrome (CRPS) and causalgia. In contrast to SCS, DRG-S also shows promise in treating conditions that are not purely neuropathic such as axial low back pain, which has a prominent nociplastic pain component. It is not known to what extent the effectiveness of DRG-S for such indications is due to effective treatment of the neuropathic pain component versus the effects of DRG-S on mechanical pain. Although rarely studied, reporting outcomes of DRG-S to treat predominantly mechanical/nociceptive pain may help point toward expanding the utility of this therapy. Here, we present five cases of refractory mechanical pain treated with DRG-S. METHODS: A retrospective analysis of all patients who underwent a successful DRG-S trial and implant between September 2017 and September 2021 at our institute was performed. Patients who had intractable joint pain without strong evidence of neuropathic pain were included in this case series. The Budapest criteria for CRPS, the Douleur Neuropathique 4 Questions (DN4) survey, or a definable nerve injury were used to determine the presence of neuropathic pain. Baseline assessments for pain (Numeric Rating Scale [NRS]), function (Oswestry Disability Index [ODI]), quality of life (EuroQol-5 Dimension [EQ-5D]), and other applicable joint surveys were extracted from pre-trial baseline and follow-up appointments. RESULTS: Five patients were identified and included. Patient diagnoses consisted of refractory joint pain of the hip, knee, or ankle. Mean NRS pain scores improved by 74% from 9.2 at baseline to 2.4 at the last follow-up (mean = 28 months post-implant). From baseline to the last follow-up, mean ODI scores improved by 65% from 66 to 23 and EQ-5D scores more than doubled from an average of 0.371 to 0.797. CONCLUSION: This clinical report illustrates the potential utility DRG-S has in treating pain that clinically presents as predominantly refractory mechanical joint pain without a significant neuropathic component. The physiological reasons for our observations may be that DRG-S is able to directly influence the conduction of nociceptive signaling at the DRG and within the spinal cord. Further investigations are warranted to determine if DRG-S is a potential treatment option for chronic mechanical pain.

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

INTRODUCTION: Spinal cord stimulation (SCS) can provide long-term pain relief for various chronic pain conditions, but some patients have no relief with trial stimulation or lose efficacy over time. To "salvage" relief in patients who do not respond or have lost efficacy, alternative stimulation paradigms or anatomical targets can be considered. Dorsal root ganglion stimulation (DRG-S) has a different mechanism of action and anatomical target than SCS. OBJECTIVES: We assessed DRG-S salvage therapy outcomes in patients who did not respond to SCS or had lost SCS efficacy. MATERIALS AND METHODS: We retrospectively included consecutive patients from 2016 to 2020 who were salvaged with DRG-S after failed SCS trials (<50% pain reduction) or who had lost efficacy after permanent SCS. We compared numerical rating scale (NRS) pain, Oswestry disability index (ODI), health-related quality of life (EuroQol five-dimensions five-level), and oral morphine equivalent (OME) opioid requirements before DRG-S salvage and at patients' last follow-up. RESULTS: A total of 60 patients who had failed SCS were salvaged with DRG-S. The mean age was 56 ± 12 years, and the most common diagnoses were complex regional pain syndrome (n = 24) and failed back surgery syndrome (n = 24). The most common failed modalities included tonic (n = 32), Burst (n = 18), and high-frequency (n = 10) SCS. The median follow-up duration of salvage DRG-S was 34 months. With DRG-S, NRS decreased (8.7 ± 1.2 to 3.8 ± 2.1), and OME declined (median 23 mg to median 15 mg), whereas EuroQol 5D scores increased (0.40 ± 0.15 to 0.71 ± 0.15), and ODI improved (64 ± 14% to 31 ± 18%) (all p < 0.05). CONCLUSIONS: DRG-S can be used in patients with chronic pain who have previously failed to receive persistent benefit from SCS.

Embodied Metarepresentations.

Meaning has been established pervasively as a central concept throughout disciplines that were involved in cognitive revolution. Its metaphoric usage comes to be, first and foremost, through the interpreter's constraint: representational relationships and contents are considered to be in the "eye" or mind of the observer and shared properties among observers themselves are knowable through interlinguistic phenomena, such as translation. Despite the instability of meaning in relation to its underdetermination by reference, it can be a tertium comparationis or "third comparator" for extended human cognition if gauged through invariants that exist in transfer processes such as translation, as all languages and cultures are rooted in pan-human experience and, thus, share and express species-specific ontology. Meaning, seen as a cognitive competence, does not stop outside of the body but extends, depends, and partners with other agents and the environment. A novel approach for exploring the transfer properties of some constituent items of the original natural semantic metalanguage in English, that is, semantic primitives, is presented: FrameNet's semantic frames, evoked by the primes SEE and FEEL, were extracted from EuroParl, a parallel corpus that allows for the automatic word alignment of items with their synonyms. Large Ontology Multilingual Extraction was used. Afterward, following the Semantic Mirrors Method, a procedure that consists back-translating into source language, a translatological examination of translated and original versions of items was performed. A fully automated pipeline was designed and tested, with the purpose of exploring associated frame shifts and, thus, beginning a research agenda on their alleged universality as linguistic features of translation, which will be complemented with and contrasted against further massive feedback through a citizen science approach, as well as cognitive and neurophysiological examinations. Additionally, an embodied account of frame semantics is proposed.

Beyond the Failure of Direct-Matching in Keyword Evaluation: A Sketch of a Graph Based Solution.

The starting point of this paper is the observation that methods based on the direct match of keywords are inadequate because they do not consider the cognitive ability of concept formation and abstraction. We argue that keyword evaluation needs to be based on a semantic model of language capturing the semantic relatedness of words to satisfy the claim of the human-like ability of concept formation and abstraction and achieve better evaluation results. Evaluation of keywords is difficult since semantic informedness is required for this purpose. This model must be capable of identifying semantic relationships such as synonymy, hypernymy, hyponymy, and location-based abstraction. For example, when gathering texts from online sources, one usually finds a few keywords with each text. Still, these keyword sets are neither complete for the text nor are they in themselves closed, i.e., in most cases, the keywords are a random subset of all possible keywords and not that informative w.r.t. the complete keyword set. Therefore all algorithms based on this cannot achieve good evaluation results and provide good/better keywords or even a complete keyword set for a text. As a solution, we propose a word graph that captures all these semantic relationships for a given language. The problem with the hyponym/hyperonym relationship is that, unlike synonyms, it is not bidirectional. Thus the space of keyword sets requires a metric that is non-symmetric, in other words, a quasi-metric. We sketch such a metric that works on our graph. Since it is nearly impossible to obtain such a complete word graph for a language, we propose for the keyword task a simpler graph based on the base text upon which the keyword sets should be evaluated. This reduction is usually sufficient for evaluating keyword sets.

Intermittent Dorsal Root Ganglion Stimulation Is as Efficacious as Standard Continuous Dosing in Treating Chronic Pain: Results From a Randomized Controlled Feasibility Trial.

INTRODUCTION: Dorsal root ganglion stimulation (DRG-S) is a form of neuromodulation used to treat chronic pain. A spinal cord stimulation (SCS) method with paresthesia-free waveform used in the dorsal columns, burst-SCS, recently demonstrated efficacy using intermittent stimulation, where stimulation is cycled on and off for set durations. Tonic SCS is a paresthesia-based therapy that is ineffective at sub-perception levels and when delivered in a cycled manner. DRG-S also uses a tonic waveform, yet unlike tonic SCS, it is effective at sub-perception levels. This study aimed to determine whether the cycling of stimulation at the DRG could maintain DRG-S efficacy. MATERIALS AND METHODS: This study followed a prospective, randomized, and balanced, double-blinded (assessor) protocol. Twenty DRG-S responders were randomized to a sequence of three programs for consecutive two-week intervals: continuous stimulation; 1 minute on:1 minute off; or 1 minute on:2 minutes off. The primary outcome of this study was change in pain ratings with the cycled programs compared with continuous stimulation. Secondary outcomes included changes in function and scores for quality of life, and stimulation program preference. RESULTS: Mean scores were similar at the end of each two-week stimulation program for Numerical Rating Scale pain (continuous = 2.9 ± 0.8, 1:1 on-off = 2.6 ± 0.7, and 1:2 on-off = 2.7 ± 0.7 cm, p = 0.39), disability (p = 0.72), and general health (p = 0.95). No clinically significant differences were found from the upper boundaries of the 95% confidence intervals of the mean difference in pain, disability, and general health for each intermittent stimulation program vs the continuous program. At the end of the study, the continuous stimulation, 1:1 on-off dosing, and 1:2 on-off dosing programs were preferred by a similar number of patients. CONCLUSIONS: Intermittent DRG-S produces comparable results to continuous stimulation over a two-week period. Intermittent delivery may extend battery life and facilitate a smaller implantable pulse generator.

Objective Improvements in Peripheral Arterial Disease from Dorsal Root Ganglion Stimulation: A Case Series.

BACKGROUND: The sympathetic nervous system (SNS) is important in the regulation of perfusion. Dorsal root ganglion stimulation (DRG-S) modulates sympathetic tone and is approved to treat complex regional pain syndrome, a disorder related to SNS dysfunction. We herein present 3 cases of DRG-S therapy to improve blood flow and symptoms of ischemia in peripheral arterial disease (PAD). METHODS: Patient 1 is a 44-year-old female with dry gangrene of the third and fourth digits of her right hand due to Raynaud's syndrome who was scheduled for amputation of the affected digits. DRG-S leads were placed at the right C6, 7, and 8 DRG. Pulse volume recordings (PVR) were measured at baseline and after DRG-S. Patient 2 is a 55-year-old female with a non-healing ulcer of her left foot secondary to PAD scheduled for a below the knee amputation who underwent a DRG-S trial with leads placed at the left L4 and L5 DRG followed by a spinal cord stimulation trial with leads placed at the T9-T10 spinal levels for comparison. Transcutaneous oximetry (TcPO2) was measured at baseline and after 3 days of each therapy. Patient 3 is a 69-year-old female with persistent left foot pain at rest secondary to PAD with DRG-S leads placed at the left L4 and S1 levels. RESULTS: All 3 patients experienced a significant reduction in pain with DRG-S, along with improvements in blood flow of the involved extremities, avoiding or limiting amputation. PVR improved dramatically with DRG-S in patient 1. A greater improvement in TcPO2 was seen with the DRG-S trial compared to spinal cord stimulation trial in patient 2. Patient 3 experienced an increase in walking distance and demonstrated long term efficacy and limb salvage at 32 months postimplantation. CONCLUSIONS: Modulation of SNS output from DRG-S through orthodromic and antidromic autonomic pathways is likely responsible for improving blood flow. DRG-S may be a treatment option for PAD.

Dorsal Root Ganglion Stimulation Normalizes Measures of Pain Processing in Patients with Chronic Low-Back Pain: A Prospective Pilot Study using Quantitative Sensory Testing.

BACKGROUND: Dorsal root ganglion stimulation (DRG-S) is used as a treatment for chronic low-back pain (CLBP), although its underlying mechanisms remain elusive. CLBP patients have been found to have reduced mechanoreceptive perception, reduced endogenous analgesia, as well as deep-tissue hyperalgesia when compared with healthy controls. Using quantitative sensory testing (QST), we studied if DRG-S in CLBP patients results in changes in pain processing. METHODS: Quantitative sensory testing was performed in patients before trial implantation of a DRG-S system for CLBP and just before the trial lead removal or at 1-month follow-up after the permanent implant. We determined the pressure pain threshold (PPT) and mechanical detection threshold (MDT) at the most painful lower-back location. PPT was also measured on the contralateral shoulder as a control. We obtained a measure of endogenous inhibitory pain modulation using conditioned pain modulation (CPM). RESULTS: We enrolled 11 patients (60 ± 16 years). Pain decreased from 8.5 ± 1.0 at baseline to 2.0 ± 1.5 on a 0-10 numerical rating scale with DRG-S (P < 0.01). From baseline to with DRG-S, PPT on the most painful location on the low back increased from 28.7 ± 13.6 to 43.4 ± 17.2 N/cm2 (P < 0.01). MDT on the same location decreased from 8.1 ± 10.4 to 3.4 ± 4.7 mN (P = 0.07). PPT on the control location and CPM did not change significantly. CONCLUSIONS: Our results suggest that DRG-S in CLBP patients reduces deep-tissue hyperalgesia in the low back, while improving mechanoreceptive perception. These changes in both neuropathic and nociceptive components of CLBP were accompanied by clinical improvements in pain and function.

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

BACKGROUND: Dorsal 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 METHODS: DRG-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. RESULTS: After 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. CONCLUSION: DRG-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.

Mechanisms for the Clinical Utility of Low-Frequency Stimulation in Neuromodulation of the Dorsal Root Ganglion.

BACKGROUND: Dorsal root ganglion stimulation (DRG-S) involves the electrical modulation of the somata of afferent neural fibers to treat chronic pain. DRG-S has demonstrated clinical efficacy at frequencies lower than typically used with spinal cord stimulation (SCS). In a clinical study, we found that the frequency of DRG-S can be tapered to a frequency as low as 4 Hz with no loss of efficacy. This review discusses possible mechanisms of action underlying effective pain relief with very low-frequency DRG-S. MATERIALS AND METHODS: We performed a literature review to explore the role of frequency in neural transmission and the corresponding relevance of frequency settings with neuromodulation. FINDINGS: Sensory neural transmission is a frequency-modulated system, with signal frequency determining which mechanisms are activated in the dorsal horn. In the dorsal horn, low-frequency signaling (<20 Hz) activates inhibitory processes while higher frequencies (>25 Hz) are excitatory. Physiologically, low-threshold mechanoreceptors (LTMRs) fibers transmit or modulate innocuous mechanical touch at frequencies as low as 0.5-5 Hz, while nociceptive fibers transmit pain at high frequencies. We postulate that very low-frequency DRG-S, at least partially, harnesses LTMRs and the native endogenous opioid system. Utilizing lower stimulation frequency decreases the total energy delivery used for DRG-S, extends battery life, and facilitates the development of devices with smaller generators.

A Survey of Text Alignment Visualization.

Text alignment is one of the fundamental techniques text-related domains like natural language processing, computational linguistics, and digital humanities. It compares two or more texts with each other aiming to find similar textual patterns, or to estimate in general how different or similar the texts are. Visualizing alignment results is an essential task, because it helps researchers getting a comprehensive overview of individual findings and the overall pattern structure. Different approaches have been developed to visualize and help making sense of these patterns depending on text size, alignment methods, and, most importantly, the underlying research tasks demanding for alignment. On the basis of those tasks, we reviewed existing text alignment visualization approaches, and discuss their advantages and drawbacks. We finally derive design implications and shed light on related future challenges.

Unilateral Dorsal Root Ganglion Stimulation Lead Placement With Resolution of Bilateral Lower Extremity Symptoms in Diabetic Peripheral Neuropathy.

Dorsal root ganglion stimulation (DRG-S) is a form of neuromodulation that can target specific dermatomes to obtain better coverage of the distal extremity. Previously proposed mechanisms of action for DRG-S focused on the dorsal root ganglion (DRG) itself, without consideration of orthodromic effects in the dorsal horn and antidromic effects on the nerve root and sympathetic chain. Diabetic peripheral neuropathy (DPN) is an axonal neuropathy that affects around half of all patients with diabetes mellitus, causing severe pain and sensory impairment in the distal extremities. We present a case of a patient with DPN in both feet, in addition to low back pain, who underwent a DRG-S trial with right T12 and S1 leads. The trial was performed unilaterally for seven days, allowing the patient to compare the treated versus the untreated (left) side. Pain, disability, general health status, and quality of life measures improved significantly. In addition to the significant pain relief in the low back and feet, the patient had near resolution of other DPN-related symptoms, including numbness, bluish discoloration, and allodynia of both feet. He also demonstrated functional and psychological benefits with only a single-sided lead. Overall, the placement of unilateral T12 and S1 DRG-S leads resulted in symmetric improvement of DPN symptoms. A possible mechanism of action is antidromic propagation of action potential signaling into the sympathetic chain to a central ganglion and then to the contralateral sympathetic chain. Given the DRG's ability to directly affect afferent sympathetic fibers with low-frequency stimulation, DRG-S may be an effective neuromodulatory treatment for DPN.

Lumbar Dorsal Root Ganglion Stimulation Lead Placement Using an Outside-In Technique in 4 Patients With Failed Back Surgery Syndrome: A Case Series.

Dorsal root ganglion stimulation (DRG-S) has shown promise as a treatment for low back pain. The traditional anterograde placement of DRG-S leads can be challenging in patients with anatomical changes from prior back surgery. We describe an "outside-in" placement technique of DRG-S leads in 4 patients with histories of multiple lumbar surgeries, which made the traditional anterograde placement not feasible. At long-term follow-up, the patients experienced substantial pain relief and improvement in quality of life, with no complications. The outside-in lead placement technique may be an efficacious alternative to the traditional techniques in patients with anomalous anatomy from prior surgery.

Lumbar Radiofrequency Ablation Interfering With S1 Dorsal Root Ganglion Stimulation Systems: Experience From Two Cases.

BACKGROUND: Dorsal root ganglion stimulation (DRG-S) has emerged as a treatment for complex regional pain syndrome (CRPS) of the lower extremities, and recent small studies are demonstrating its potential efficacy in pain syndromes that are traditionally considered nociceptive in nature, such as axial low back pain. While improvements in neuromodulation technology have been substantial over the past decade, with DRG-S systems patients occasionally require additional interventional pain treatments for treatment of pain from other sources. Radiofrequency ablation (RFA) of medial branch nerves innervating the facet joints is an accepted therapy for pain arising from the facet joints. METHODS: We describe 2 cases from the same practice where we observed similar phenomena while performing a 2-needle monopolar lumbar RFA in patients with a DRG-S system implanted with leads positioned bilaterally at the S1 DRGs. RESULTS: Initiation of RFA resulted in motor activation and discomfort in an S1 distribution in the legs in both individual cases. CONCLUSIONS: RFA can interfere with implanted DRG-S systems, resulting in overstimulation with motor recruitment. Specific anatomical considerations and device settings that may prevent interference are discussed.