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.

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.

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.

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.