Therapy Habituation at 12 Months: Spinal Cord Stimulation Versus Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome Type I and II.

The ACCURATE randomized, controlled trial compared outcomes of dorsal root ganglion (DRG) stimulation versus tonic spinal cord stimulation (SCS) in 152 subjects with chronic lower extremity pain due to complex regional pain syndrome (CRPS) type I or II. This ACCURATE substudy was designed to evaluate whether therapy habituation occurs with DRG stimulation as compared to SCS through 12-months. A modified intention-to-treat analysis was performed to assess percentage pain relief (PPR) and responder rates at follow-up visits (end-of-trial, 1, 3, 6, 9, 12-months postpermanent implant) for all subjects that completed trial stimulation (DRG:N = 73, SCS:N = 72). For both groups, mean PPR was significantly greater at end-of-trial (DRG = 82.2%, SCS =0 77.0%) than all other follow-ups. Following permanent DRG system implantation, none of the time points were significantly different from one another in PPR (range = 69.3-73.9%). For the SCS group, PPR at 9-months (58.3%) and 12-months (57.9%) was significantly less than at 1-month (66.9%). The responder rate also decreased for the SCS group from 1-month (68.1%) to 12-months (61.1%). After stratifying by diagnosis, it was found that only the CRPS-I population had diminishing pain relief with SCS. DRG stimulation resulted in more stable pain relief through 12-months, while tonic SCS demonstrated therapy habituation at 9- and 12-months. Trial Registration: The ACCURATE study was registered at ClinicalTrials.gov with Identifier NCT01923285. PERSPECTIVE: This article reports on an ACCURATE substudy, which found that long-term therapy habituation occurred at 12-months with SCS, but not DRG stimulation, in patients with CRPS. The underlying mechanisms of action for these results remain unclear, although several lines of inquiry are proposed.

Early US Experience With Stimulation of the Dorsal Root Ganglia for the Treatment of Peripheral Neuropathy in the Lower Extremities: A Multicenter Retrospective Case Series.

BACKGROUND: Peripheral neuropathy is a chronic pain disorder involving physical, chemical, or metabolic damage to peripheral nerves. Its pain can be intense and disabling. Dorsal root ganglion (DRG) stimulation is an effective treatment for neuropathic pain, including cases with the limited regional distributions that often characterize peripheral neuropathy. METHODS: A retrospective analysis was completed. Patients were included on the basis of having chronic intractable peripheral neuropathy of the legs and/or feet and responding successfully to a trial of DRG stimulation with leads at L4-S1. Visual analog scale pain scores and pain medication usage were collected at the baseline visit and after six weeks of treatment. Eight consecutive patients across two study centers were included (7 male, 1 female; mean age: 64.8 ± 10.2 years). Six cases of neuropathy were bilateral and two were unilateral. One patient presented with chronic radiculopathy, two patients had neuropathy associated with diabetes, and five patients had neuropathy not associated with a diabetes history. RESULTS: The pain was rated 7.38 ± 0.74 at baseline and decreased to 1.50 ± 1.31 at the 6-week follow-up, a reduction of 79.5 ± 18.8%. For individual patients, pain relief ranged from 42.86% to 100.00%; two patients experienced complete elimination of pain while seven of the eight patients experienced greater than 50% pain relief. In addition, three patients significantly decreased their pain medication use and four were able to discontinue their medications entirely. CONCLUSION: This small multicenter retrospective case series provides preliminary evidence that the painful symptoms of general peripheral neuropathy in the lower extremities, as well as associated pain medication usage, can be effectively managed by DRG stimulation at the L4-S1 spinal level. Importantly, this treatment appears efficacious for peripheral neuropathy.

Prospective Cohort Analysis of DRG Stimulation for Failed Back Surgery Syndrome Pain Following Lumbar Discectomy.

INTRODUCTION: Surgical lumbar discectomy is a commonly performed routine spinal procedure that is usually undertaken to alleviate lumbar radicular symptoms caused by a herniated intervertebral disc. Surgical lumbar discectomy can also lead to chronic postsurgical leg and/or back pain (failed back surgery syndrome [FBSS]), a condition that can be refractory to conventional medical management. Early clinical results on the use of dorsal root ganglion (DRG) stimulation for FBSS have supported the use of this treatment alternative. METHODS: A multicenter, single-arm, observational cohort study enrolled patients who had chronic pain following surgical lumbar discectomy, had failed conservative treatments, and reported pain intensity of at least 6 out of 10 in the primary region of pain. Data were collected on pain, quality of life, disability, and mood at baseline and through 12 months. RESULTS: Thirteen patients underwent a trial of DRG stimulation; 11 (84.6%; 95% confidence interval = 57.8% to 95.7%) had good outcomes and underwent permanent device placement. Pain was reduced from a score of 8.64 (±0.92) at baseline to 2.40 (±2.38; n = 9) after 12 months of treatment, a 72.05% average reduction (P < 0.001). Similar improvements were observed across the secondary clinical measures, and safety data were in line with published rates. DISCUSSION: These results suggest that DRG stimulation induces pain relief in subjects diagnosed with FBSS. These reductions in pain were also associated with improvements in quality of life and disability. Additional prospective studies are warranted to further investigate this potential application of DRG stimulation, as well as to optimize patient selection, lead placement, and programming strategies.

A Review of Spinal and Peripheral Neuromodulation and Neuroinflammation: Lessons Learned Thus Far and Future Prospects of Biotype Development.

BACKGROUND: There is increasing literature evidence both clinically and experimentally on the existence of potent, adaptive interactions between the central and peripheral aspects of the neuroimmune system in the genesis and maintenance of chronic neuropathic extremity pain and nociceptive back pain. The neuroinflammatory pathways are modulated by the interaction of pro- and anti-inflammatory cytokines and chemokines, which are released by peripheral immune system-derived cell species (macrophages and leukocytes). This review examines the possible impact of spinal and peripheral neurostimulation on the inflammatory response in the context of acute and chronic pain pathologies of different origin. STUDY DESIGN: A narrative review of preclinical and clinical studies addressed to the spinal cord and peripheral nerve stimulation and neuroinflammation. METHODS: Available literature was reviewed on neurostimulation technologies and both acute and chronic low-grade inflammation to identify primary outcome measures and to provide an overview of postulated mechanisms of action of neurostimulation on host inflammatory responses. Data sources included relevant literature identified through searches of PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles. RESULTS: A comprehensive review of the literature indicates an alternate or synergistic mechanism of action of neurostimulation, beyond modulating somatosensory pain pathways, in modifying inflammatory response associated with chronic pain, by promoting a systemic anti-inflammatory state with upregulation of anti-inflammatory mediators. CONCLUSIONS: These preliminary findings may have important implications on the potential applications of neurostimulation as an anti-inflammatory therapy and the role of molecular profiling as a preimplant screening modality and post-implant outcome validation. Thus, future targeted clinical and experimental research is highly warranted in this particular novel field of neuromodulation.