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Burst Spinal Cord Stimulation as Compared With L2 Dorsal Root Ganglion Stimulation in Pain Relief for Nonoperated Discogenic Low Back Pain: Analysis of Two Prospective Studies

  • Martijn R. Mons
    Correspondence
    Address correspondence to: Martijn R. Mons, MSc, Universiteitssingel 40, 6229 ER, The Netherlands.
    Affiliations
    Department of Anesthesiology and Pain Management, University Pain Clinic Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands

    Department of Translational Neuroscience, School for Mental Health and Neuroscience, University of Maastricht, Maastricht, The Netherlands
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  • Kenneth B. Chapman
    Affiliations
    Department of Anesthesiology, New York University Langone Medical Center, New York, NY, USA

    Department of Anesthesiology, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
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  • Chris Terwiel
    Affiliations
    Department of Anesthesiology and Pain Management Arnhem, Rijnstate Hospital, Arnhem, The Netherlands
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  • Elbert A. Joosten
    Affiliations
    Department of Anesthesiology and Pain Management, University Pain Clinic Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands

    Department of Translational Neuroscience, School for Mental Health and Neuroscience, University of Maastricht, Maastricht, The Netherlands
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  • Jan Willem Kallewaard
    Affiliations
    Department of Anesthesiology and Pain Management Arnhem, Rijnstate Hospital, Arnhem, The Netherlands

    Department of Anesthesiology and Pain Management, Amsterdam University Medical Center, Amsterdam, The Netherlands
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Open AccessPublished:May 16, 2023DOI:https://doi.org/10.1016/j.neurom.2023.04.464

      Abstract

      Introduction

      Chronic discogenic low back pain (CD-LBP) is caused by degenerated disks marked by neural and vascular ingrowth. Spinal cord stimulation (SCS) has been shown to be effective for pain relief in patients who are not responsive to conventional treatments. Previously, the pain-relieving effect of two variations of SCS has been evaluated in CD-LBP: Burst SCS and L2 dorsal root ganglion stimulation (DRGS). The aim of this study is to compare the effectivity in pain relief and pain experience of Burst SCS with that of conventional L2 DRGS in patients with CD-LBP.

      Materials and Methods

      Subjects were implanted with either Burst SCS (n = 14) or L2 DRGS with conventional stimulation (n = 15). Patients completed the numeric pain rating score (NRS) for back pain and Oswestry disability index (ODI) and EuroQoL 5D (EQ-5D) questionnaires at baseline, and at three, six, and 12 months after implantation. Data were compared between time points and between groups.

      Results

      Both Burst SCS and L2 DRGS significantly decreased NRS, ODI, and EQ-5D scores as compared with baseline. L2 DRGS resulted in significantly lower NRS scores at 12 months and significantly increased EQ-5D scores at six and 12 months.

      Conclusions

      Both L2 DRGS and Burst SCS resulted in reduction of pain and disability, and increased quality of life in patients with CD-LBP. L2 DRGS provided significantly increased pain relief and improvement in quality of life when compared with Burst SCS.

      Clinical Trial Registration

      The clinical trial registration numbers for the study are NCT03958604 and NL54405.091.15.

      Keywords

      Introduction

      Chronic discogenic low back pain (CD-LBP) is a condition caused by a damaged or degenerated intervertebral disk (IVD). This degeneration is marked by loss of disk height, ingrowth of sensory neurons, and development of an inflammatory environment inside the disk, causing chronic pain.
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      Recently, several promising publications applied neurostimulation for nonoperative LBP, which included patients with CD-LBP, but did not specifically target patients with CD-LBP.
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      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      • Alo K.M.
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      • Redko V.
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      • Naumann C.
      Lumbar and sacral nerve root stimulation (NRS) in the treatment of chronic pain: a novel anatomic approach and neuro stimulation technique.
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      • Haroon A.
      Metabolic imaging of pain matrix using 18 F fluoro-deoxyglucose positron emission tomography/computed tomography for patients undergoing L2 dorsal root ganglion stimulation for low back pain.
      • Al-Kaisy A.
      • Palmisani S.
      • Smith T.E.
      • et al.
      Long-term improvements in chronic axial low back pain patients without previous spinal surgery: A cohort analysis of 10-kHz high-frequency spinal cord stimulation over 36 months.
      • Vallejo R.
      • Zevallos L.M.
      • Lowe J.
      • Benyamin R.
      Is spinal cord stimulation an effective treatment option for discogenic pain?.
      These studies used conventional spinal cord stimulation (SCS) (con-SCS)
      • Al-Kaisy A.
      • Palmisani S.
      • Smith T.E.
      • et al.
      Long-term improvements in chronic axial low back pain patients without previous spinal surgery: A cohort analysis of 10-kHz high-frequency spinal cord stimulation over 36 months.
      ,
      • Vallejo R.
      • Zevallos L.M.
      • Lowe J.
      • Benyamin R.
      Is spinal cord stimulation an effective treatment option for discogenic pain?.
      in addition to dorsal root ganglion stimulation (DRGS).
      • Kallewaard J.W.
      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      • Alo K.M.
      • Yland M.J.
      • Redko V.
      • Feler C.
      • Naumann C.
      Lumbar and sacral nerve root stimulation (NRS) in the treatment of chronic pain: a novel anatomic approach and neuro stimulation technique.
      • Mehta V.
      • Bouchareb Y.
      • Ramaswamy S.
      • Ahmad A.
      • Wodehouse T.
      • Haroon A.
      Metabolic imaging of pain matrix using 18 F fluoro-deoxyglucose positron emission tomography/computed tomography for patients undergoing L2 dorsal root ganglion stimulation for low back pain.
      Although these studies have shown con-SCS to be effective, novel forms of stimulation could provide enhanced pain relief. In 2010, De Ridder et al
      • de Ridder D.
      • Vanneste S.
      • Plazier M.
      • van der Loo E.
      • Menovsky T.
      Burst spinal cord stimulation: toward paresthesia-free pain suppression.
      introduced a passive recharge burst pattern waveform that was free of paresthesia sensation (referred to in this article as Burst SCS). It was in 2017 that Burst SCS was found to be superior to con-SCS in patients with chronic pain of the trunk and/or limbs.
      • Deer T.
      • Slavin K.V.
      • Amirdelfan K.
      • et al.
      Success using neuromodulation with BURST (SUNBURST) study: results from a prospective, randomized controlled trial using a novel burst waveform.
      Using the Burst waveform in an SCS pilot study for the treatment of CD-LBP, our group showed promising improvements in pain and function, resulting in significant reduction of back and leg pain in patients with CD-LBP and decrease in the level of disability.
      • Mons M.R.
      • Chapman K.B.
      • Terwiel C.
      • Joosten E.A.
      • Kallewaard J.W.
      A prospective study of BurstDRTM spinal cord stimulation for non-operated discogenic low back pain.
      DRGS is a direct spin-off of SCS, which places an electrical field near the somata of afferent nerve fibers.
      • Liem L.
      • Russo M.
      • Huygen F.J.P.M.
      • et al.
      A multicenter, prospective trial to assess the safety and performance of the spinal modulation dorsal root ganglion neurostimulator system in the treatment of chronic pain.
      Receiving its Conformité Européenne mark in 2013 and US Food and Drug Administration approval in 2015, DRGS was designed for the treatment of focal pain, although there have been multiple indications of the efficacy of DRGS in multidermatomal pain syndromes, including LBP.
      • Huygen F.
      • Liem L.
      • Cusack W.
      • Kramer J.
      Stimulation of the L2–L3 dorsal root ganglia induces effective pain relief in the low back.
      • Deer T.R.
      • Levy R.M.
      • Kramer J.
      • et al.
      Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial.
      • D’Souza R.S.
      • Kubrova E.
      • Her Y.F.
      • et al.
      Dorsal root ganglion stimulation for lower extremity neuropathic pain syndromes: an evidence-based literature review.
      DRGS has also been used for nonoperative LBP and was studied prospectively in the treatment of CD-LBP.
      • Kallewaard J.W.
      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      Con-SCS is believed to use the pain gate theory mechanistically, with antidromic stimulation of dorsal columns Aβ-fibers to modulate nociceptive signaling in the dorsal horn.
      • Joosten E.A.
      • Franken G.
      Spinal cord stimulation in chronic neuropathic pain: mechanisms of action, new locations, new paradigms.
      DRGS is thought to modulate nociceptive signals locally at the dorsal root ganglion (DRG) for focal pain, and multidermatomal coverage potentially though convergence and orthodromic propagation of signals into the dorsal horn.
      • Joosten E.A.
      • Franken G.
      Spinal cord stimulation in chronic neuropathic pain: mechanisms of action, new locations, new paradigms.
      ,
      • Koopmeiners A.S.
      • Mueller S.
      • Kramer J.
      • Hogan Q.H.
      Effect of electrical field stimulation on dorsal root ganglion neuronal function.
      Innervation of the lumbar disks has been shown to travel through the sympathetic nervous system, converging at the L2 level.
      • Ohtori S.
      • Takahashi K.
      • Chiba T.
      • Yamagata M.
      • Sameda H.
      • Moriya H.
      Sensory innervation of the dorsal portion of the lumbar intervertebral discs in rats.
      • Nakamura S.I.
      • Takahashi K.
      • Takahashi Y.
      • Morinaga T.
      • Shimada Y.
      • Moriya H.
      Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats.
      • Aoki Y.
      • Takahashi Y.
      • Takahashi K.
      • et al.
      Sensory innervation of the lateral portion of the lumbar intervertebral disc in rats.
      • Morinaga T.
      • Takahashi K.
      • Yamagata M.
      • et al.
      Sensory innervation to the anterior portion of lumbar intervertebral disc.
      • Quinones S.
      • Konschake M.
      • Aguilar L.L.
      • et al.
      Clinical anatomy of the lumbar sinuvertebral nerve with regard to discogenic low back pain and review of literature.
      • Breemer M.C.
      • Malessy M.J.A.
      • Notenboom R.G.E.
      Origin, branching pattern, foraminal and intraspinal distribution of the human lumbar sinuvertebral nerves.
      Huygen et al
      • Huygen F.
      • Liem L.
      • Cusack W.
      • Kramer J.
      Stimulation of the L2–L3 dorsal root ganglia induces effective pain relief in the low back.
      first studied L2 DRGS lead placement in LBP with good but mixed results because seven patients had >50% pain relief, whereas five had poor results. We refined the study criteria from these data and proposed L2 DRGS for CD-LBP, excluding patients who responded to medial branch blocks and sacroiliac joint injections and who subsequently had a positive discogram result. This prospective study used DRGS at L2 to treat CD-LBP, resulting in significant, maintained improvements in pain, function, and quality of life.
      • Kallewaard J.W.
      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      The increased availability of new waveforms for pain treatment in CD-LBP warrants an evaluation of their effectivity in helping to choose the optimal therapy. In previous research, we studied the efficacy of both L2 DRGS and Burst SCS in independent studies for the treatment of CD-LBP, using the same inclusion and exclusion criteria in similar patient populations.
      • Kallewaard J.W.
      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      ,
      • Mons M.R.
      • Chapman K.B.
      • Terwiel C.
      • Joosten E.A.
      • Kallewaard J.W.
      A prospective study of BurstDRTM spinal cord stimulation for non-operated discogenic low back pain.
      The aim of this analysis is to compare the effectivity of Burst SCS with that of L2 DRGS in pain relief, function, and quality of life in patients with CD-LBP.

      Materials and Methods

      This study analyzed data from two separate prospective studies with similar CD-LBP populations, using identical inclusion and exclusion criteria.
      • Kallewaard J.W.
      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      ,
      • Mons M.R.
      • Chapman K.B.
      • Terwiel C.
      • Joosten E.A.
      • Kallewaard J.W.
      A prospective study of BurstDRTM spinal cord stimulation for non-operated discogenic low back pain.
      The Burst SCS study was conducted from June 2019 to December 2021 and the L2 DRGS study from November 2015 to November 2017, both in the Rijnstate Hospital, The Netherlands. The trials were conducted by the same staff. Both trial protocols were approved by the local medical ethics committee Arnhem-Nijmegen (trial reference numbers: NL67172.091.18 and NL54405.091.1), and all participants gave written informed consent.
      Pre- and postprocedure protocols were identical in the studies and are available in these works.
      • Kallewaard J.W.
      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      ,
      • Mons M.R.
      • Chapman K.B.
      • Terwiel C.
      • Joosten E.A.
      • Kallewaard J.W.
      A prospective study of BurstDRTM spinal cord stimulation for non-operated discogenic low back pain.
      Implant procedures of DRGS and SCS were according to international protocol.
      • Chapman K.B.
      • Spiegel M.A.
      • Dickerson D.M.
      • et al.
      A paramedian approach for dorsal root ganglion stimulation placement developed to limit lead migration and fracture.
      For the Burst SCS study, patients (n = 14) were implanted using two eight-contact ”Octrode” epidural leads and programmed with the BurstDR stimulation paradigm (Proclaim™, Abbott; Plano, TX). Briefly, the left electrode tip was placed at T8, and the right tip was placed at T9; no intraoperative testing was performed. For the L2 DRGS study, patients (n = 15) were implanted with a four-contact 50-cm MN 20550-50 lead (Spinal Modulation, Inc, Menlo Park, CA) placed over the L2 DRG and an Axium Mn 20200 internal pulse generator (Spinal Modulation, Inc). During intraoperative testing, all patients reported paresthesia coverage of the painful region.
      Burst SCS stimulation settings were 40 Hz interburst frequency, 500 Hz intraburst frequency of five pulses, 1-millisecond pulse width, and 1.3 to 0.6 mA with on/off cycling. Amplitudes were adjusted to 60% of threshold levels. Average and individual burst cycling settings are presented in Supplementary Data Tables S1 and S2. L2 DRGS stimulation settings ranged from 4 to 40 Hz frequency and between 100 and 420 milliseconds pulse width, and then reduced to subthreshold levels. Individual and average DRGS stimulation parameters are displayed in Supplementary Data Tables S3 and S4.
      For both studies, patients completed the numeric pain rating score (NRS) as an index of pain,
      • Perrot S.
      • Lantéri-Minet M.
      Patients’ Global impression of Change in the management of peripheral neuropathic pain: clinical relevance and correlations in daily practice.
      at baseline, after implantation trial, and, with a positive trial, at three, six, and 12 months after implantation. As a measure of disability, the Oswestry Disability Index (ODI)
      • Fairbank J.C.T.
      • Pynsent P.B.
      The Oswestry disability index.
      was completed, and as a measure of quality of life and health status, the EuroQoL 5D (EQ-5D)–3L or EQ-5D-5L
      • Devlin N.J.
      • Brooks R.
      EQ-5D and the EuroQol Group: past, present and future.
      ,
      • Rabin R.
      • de Charro F.
      EQ-5D: A measure of health status from the EuroQol Group.
      was used. Both were completed at baseline and at three, six, and 12 months after implantation. Only data on matching follow-up moments between the two studies are reported in this study.
      Differences between time points of Burst SCS and L2 DRGS treatments were assessed using (non) parametric unpaired t-tests (GraphPad Prism). Differences between patient demographics were assessed using unpaired t-tests or chi-square test. Unless otherwise stated, error is displayed as SEM. Only data regarding patients who received permanent implants were evaluated.

      Results

      Baseline characteristics did not differ between the patient populations with CD-LBP stimulated with either Burst SCS or L2 DRGS (Table 1). This analysis indicates that NRS scores are significantly lower (54%) for L2 DRGS (22.9 ± 5.7) than for Burst SCS (42.5 ± 5.2) after 12 months (p = 0.018) (Fig. 1). EQ-5D-5L scores were significantly increased at six (p = 0.013) and 12 months (p = 0.003) for L2 DRGS (0.82 ± 0.04, 0.84 ± 0.03) compared with Burst SCS (0.68 ± 0.04, 0.67 ± 0.04). No significant differences between Burst SCS and L2 DRGS were detected regarding ODI (Fig. 2). Burst SCS in addition to L2 DRGS significantly decreased NRS, ODI, and EQ-5D-5L rates over time, compared with baseline.
      • Kallewaard J.W.
      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      ,
      • Mons M.R.
      • Chapman K.B.
      • Terwiel C.
      • Joosten E.A.
      • Kallewaard J.W.
      A prospective study of BurstDRTM spinal cord stimulation for non-operated discogenic low back pain.
      Data regarding the development of NRS, ODI and EQ-5D scores are presented in Table 2 and Supplementary Data Figures S1 to S6.
      Table 1Baseline Characteristics.
      CharacteristicBurst SCSDRGSp Value
      Age, y, ± SD47.5 ± 13.449.0 ± 10.70.74
      Sex, N (%)0.65
      Male4 (27%)8 (57%)
      Female11 (73%)6 (43%)
      BMI26.2 ± 4.726.4 ± 3.80.92
      Level of painful disk
      N (%)
      L3–L43 (18.8%)1 (4.6%)
      L4–L57 (43.7%)9 (40.9%)
      L5–S16 (37.5%)12 (54.6%)
      Duration of discogenic LBP, y9.0 ± 9.08.5 ± 1.40.83
      BMI, body mass index.
      Figure thumbnail gr1
      Figure 1NRS scores for CD-LBP. DRGS provides significantly more CD-LBP relief at 12 months. Error bars display SEM.
      Figure thumbnail gr2
      Figure 2Oswestry Disability Index scores. Burst SCS and DRGS result in similar ODI scores. Error bars display SEM.
      Table 2Study Results.
      Statistical significance p < 0.05.
      QuestionnaireInterventionBaselineTrial3 mo6 mo12 mo
      NRS ± SEMBurst SCS71.7 ± 2.0p = 0.9108.2 ± 2.2p = 0.09432.9 ± 6.0p = 0.51843.4 ± 6.3p = 0.07342.5 ± 5.2p = 0.018
      Statistical significance p < 0.05.
      L2 DRGS71.3 ± 3.416.7 ± 4.126.9 ± 6.126 ± 6.822.9 ± 5.7
      ODI ± SEMBurst SCS42.1 ± 3.5p = 0.93325.0 ± 3.1p = 0.52625.8 ± 2.7p = 0.311
      L2 DRGS41.7 ± 3.321.6 ± 4.220.1 ± 4.4
      EQ-5D ± SEMBurst SCS0.5 ± 0.05p = 0.0980.7 ± 0.02p = 0.3600.7 ± 0.04p = 0.012
      Statistical significance p < 0.05.
      0.7 ± 0.04p = 0.003
      Statistical significance p < 0.05.
      L2 DRGS64.7 ± 5.176.1 ± 4.078.7 ± 3.176.6 ± 3.3
      Statistical significance p < 0.05.

      Discussion

      This comparison of two prospective studies using neuromodulation for treatment of patients with CD-LBP indicates that L2 DRGS may be a better long-term treatment option than Burst SCS for CD-LBP. There may be inherent challenges that influence validity when comparing clinical studies for similar diagnoses, such as inclusion and exclusion criteria, age, sex, and cultural/social differences within patient populations. However, these two prospective pilot studies used a nearly identical inclusion criterion, patient populations, were performed by the same team, and measured the same outcomes. Both studies indicated a clinically significant efficacy in pain relief, function based on the ODI, and improvements in quality of life.

      Pain Relief

      Both Burst SCS and L2 DRGS were effective in the treatment of pain in patients with CD-LBP at all follow-up time points.
      • Kallewaard J.W.
      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      ,
      • Mons M.R.
      • Chapman K.B.
      • Terwiel C.
      • Joosten E.A.
      • Kallewaard J.W.
      A prospective study of BurstDRTM spinal cord stimulation for non-operated discogenic low back pain.
      Although both groups showed early success, at 12 months, the L2 DRGS group revealed significantly improved pain relief of 22.9 on the NRS, on which Burst SCS pain relief only reached 42.5. In addition, pain relief associated with L2 DRGS remained stable after three months, whereas with Burst SCS, a trend of decreasing pain relief was shown after three months, eventually leading to statistical significance between the two treatments at 12 months (Fig. 1) (Table 2).

      Quality of Life

      Both Burst SCS and L2 DRGS also showed clinically significant differences in quality of life in treating CD-LBP.
      • Kallewaard J.W.
      • Edelbroek C.
      • Terheggen M.
      • Raza A.
      • Geurts J.W.
      A prospective study of dorsal root ganglion stimulation for non-operated discogenic low back pain.
      ,
      • Mons M.R.
      • Chapman K.B.
      • Terwiel C.
      • Joosten E.A.
      • Kallewaard J.W.
      A prospective study of BurstDRTM spinal cord stimulation for non-operated discogenic low back pain.
      After parallel improvement up to the three-month point, DRGS resulted in significantly increased quality of life compared with Burst SCS at six and 12 months (Fig. 3) (Table 2).
      Figure thumbnail gr3
      Figure 3EQ-5D quality-of-life score. Burst SCS and DRGS result in similar EQ-5D rates. Error bars display SEM.

      Effects on Function and Disability

      Both groups experienced statistically significant decreases in disability based on the ODI; there was no statistical significance between the treatments (Fig. 2) (Table 2).

      Longevity of Therapy

      Our data show a gradual increase in pain and gradual decrease in quality of life in the Burst SCS cohort starting at three months in contrast to L2 DRGS. Although underlying causation is unclear, we surmise that L2 DRGS may be more robust against loss of efficacy. This is supported by clinical evidence that indicated that in a pooled analysis of 249 DRGS cases, only a few explants were owing to inadequate pain relief, contrasting with the higher rates of explantation secondary to inadequate pain relief in SCS literature.
      • Chapman K.B.
      • Yang A.
      • Mogilner A.Y.
      • et al.
      Dorsal root ganglion stimulation device explantation: a multicenter pooled data analysis.
      • Dupré D.A.
      • Tomycz N.
      • Whiting D.
      • Oh M.
      Spinal cord stimulator explantation: motives for removal of surgically placed paddle systems.
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      • Aner M.
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      • Gill J.S.
      Explantation of percutaneous spinal cord stimulator devices: a retrospective descriptive analysis of a Single-Center 15-year experience.
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      A Spinal cord stimulation service review from a single centre using a single manufacturer over a 7.5 year follow-up period.
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      Explantation rates of high frequency spinal cord stimulation in two outpatient clinics.

      Context

      Previous works have evaluated both SCS and DRGs in prospective clinical settings, providing evidence for the success of these interventions in CD-LBP.
      • Mehta V.
      • Bouchareb Y.
      • Ramaswamy S.
      • Ahmad A.
      • Wodehouse T.
      • Haroon A.
      Metabolic imaging of pain matrix using 18 F fluoro-deoxyglucose positron emission tomography/computed tomography for patients undergoing L2 dorsal root ganglion stimulation for low back pain.
      ,
      • Vallejo R.
      • Zevallos L.M.
      • Lowe J.
      • Benyamin R.
      Is spinal cord stimulation an effective treatment option for discogenic pain?.
      ,
      • Mehta V.
      • Poply K.
      • Ahmad A.
      • et al.
      Effectiveness of high dose spinal cord stimulation for non-surgical intractable lumbar radiculopathy - HIDENS Study.
      Differences between patient populations make it difficult to directly compare these works with the data described in this study. Our report is a step toward evaluating the differences between these treatment options.
      We hypothesize that the mechanisms of action that underlie DRGS at L2 are responsible for our findings. As stated earlier, innervation of the ventrolateral IVDs and vertebral bodies occurs through fibers running in the sympathetic chain that converge at the L2 DRG.
      • Ohtori S.
      • Takahashi K.
      • Chiba T.
      • Yamagata M.
      • Sameda H.
      • Moriya H.
      Sensory innervation of the dorsal portion of the lumbar intervertebral discs in rats.
      • Nakamura S.I.
      • Takahashi K.
      • Takahashi Y.
      • Morinaga T.
      • Shimada Y.
      • Moriya H.
      Origin of nerves supplying the posterior portion of lumbar intervertebral discs in rats.
      • Aoki Y.
      • Takahashi Y.
      • Takahashi K.
      • et al.
      Sensory innervation of the lateral portion of the lumbar intervertebral disc in rats.
      • Morinaga T.
      • Takahashi K.
      • Yamagata M.
      • et al.
      Sensory innervation to the anterior portion of lumbar intervertebral disc.
      Stimulation at the L2 DRG allows direct modulation of fibers transmitting CD-LBP by increasing its natural signal filtering effects.
      • Koopmeiners A.S.
      • Mueller S.
      • Kramer J.
      • Hogan Q.H.
      Effect of electrical field stimulation on dorsal root ganglion neuronal function.
      ,
      • Kent A.R.
      • Min X.
      • Hogan Q.H.
      • Kramer J.M.
      Mechanisms of dorsal root ganglion stimulation in pain suppression: a computational modeling analysis.
      ,
      • Esposito M.F.
      • Malayil R.
      • Hanes M.
      • Deer T.
      Unique characteristics of the dorsal root ganglion as a target for neuromodulation.
      In contrast, modulation of the dorsal columns via SCS occurs through a circuitous, multisynaptic path, targeting nonnociceptive dorsal column fibers and antidromically modulating the spinal nociceptive network to effect sympathetic transmission.
      • Joosten E.A.
      • Franken G.
      Spinal cord stimulation in chronic neuropathic pain: mechanisms of action, new locations, new paradigms.
      ,
      • Smits H.
      • van Kleef M.
      • Joosten E.A.
      Spinal cord stimulation of dorsal columns in a rat model of neuropathic pain: evidence for a segmental spinal mechanism of pain relief.
      This may result in less specific targeting and blocking of the nociceptive C and Aδ fibers involved in CD-LBP.

      Limitations

      Although this analysis presents what we believe is the first insight into efficacy of L2 DRGS compared with Burst SCS in the treatment of patients with nonoperated CD-LBP, its limitations must be noted. These are small prospective studies that cannot be compared with large randomized controlled trials, which are a more definitive means of comparing treatments. In addition, research has shown that lower Burst SCS amplitudes may result in increased pain relief.
      • Leong S.L.
      • de Ridder D.
      • Deer T.
      • Vanneste S.
      Potential therapeutic effect of low amplitude burst spinal cord stimulation on pain.
      However, because this has not yet been widely introduced in the clinic, this study reflects the current state of Burst SCS programming. Moreover, it is now common practice to standardize the cycling programs for Burst SCS, which was not previously the case.
      • Deer T.R.
      • Patterson D.G.
      • Baksh J.
      • et al.
      Novel intermittent dosing burst paradigm in spinal cord stimulation.
      Burst SCS has an established effect on the affective component of pain via the medial pathway, and we did not measure this.
      • de Ridder D.
      • Plazier M.
      • Kamerling N.
      • Menovsky T.
      • Vanneste S.
      Burst spinal cord stimulation for limb and back pain.
      • Hagedorn J.M.
      • Falowski S.M.
      • Blomme B.
      • Capobianco R.A.
      • Yue J.J.
      Burst spinal cord stimulation can attenuate pain and its affective components in chronic pain patients with high psychological distress: results from the prospective, international TRIUMPH study.
      • Yearwood T.
      • de Ridder D.
      • Yoo H.B.
      • et al.
      Comparison of neural activity in chronic pain patients during tonic and burst spinal cord stimulation using fluorodeoxyglucose positron emission tomography.
      • de Ridder D.
      • Vanneste S.
      Burst and tonic spinal cord stimulation: different and common brain mechanisms.
      Translational preclinical studies are needed to provide further mechanistic insight into the possible differences in mechanism of action between L2 DRGS and Burst SCS.

      Conclusions

      Comparison of two small-scale patient cohorts shows that L2 DRGS provided better long-term pain relief and increases in quality of life than did Burst SCS for patients with CD-LBP. Patients treated with L2 DRGS show significantly more pain relief at 12 months than do those treated with Burst SCS, and increased quality of life at six and 12 months.

      Authorship Statements

      Martijn R. Mons wrote the manuscript and performed data analysis; Jan-Willem Kallewaard designed and conducted the study, including patient recruitment; Chris Terwiel conducted the study, recruited patients, and performed data collection; Jan-Willem Kallewaard, Kenneth B. Chapman, and Elbert A. Joosten provided editorial support. All authors approved the final version of the manuscript.

      Supplementary Data

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