Neurostimulation for Neuropathic Pain: Outcomes and New Paradigms
Transcription
Neurostimulation for Neuropathic Pain: Outcomes and New Paradigms
® XXI5••NO 1 • JUNE 2013 VOL XXIIIVOL • NO SEPTEMBER 2015 Neurostimulation forVol.ÊXXI,ÊIssueÊ1Ê Neuropathic Pain: Editorial Board and New Paradigms Outcomes N Editor-in-Chief europathic pain afflicts JaneÊC.ÊBallantyne,ÊMD,ÊFRCA millions of people globAnesthesiology,ÊPainÊMedicine USA ally and presents a major health AdvisoryÊBoard and economic bur- den.MichaelÊJ.ÊCousins,ÊMD,ÊDSC Epidemiological studies carried out withPainÊMedicine,ÊPalliativeÊMedicine validated screening tools estimate Australia that as many as 7–8% of adults in the JuneÊ2013 PsychosocialÊAspectsÊofÊChronicÊPelvicÊPain alternative therapeutic strategies for recommendation based on a systematic review and meta-analysis of published patients with neuropathic pain. and unpublished clinical trials.15 Data Pain is unwanted, is unfortunately common, and remains for survival (i.e., Spinal Cordessential Stimulation evading danger) and facilitating medical diagnoses. This complex amalgamation of management of patients with chronic Spinal cord (SCS) as is a a motisensation, emotions, and thoughts manifests itself as stimulation pain behavior. Pain neuropathic painfor is physician challenging, with 1therapy for chronic pain was introand for emergency department visits and is vating factor consultations from these studies suggest that the more than 50% of patients experiencing duced nearly half a century ago by general population have pain with neu- only partial or no relief of their pain. In Norman Shealy and colleagues. Recent ropathic characteristics.47 Neuropathic addition, the adverse effects associated advances in percutaneous implantation pain can result from various etiologies, with the drugs used to manage the pain techniques and devices, technological such as traumatic or surgical injuries to may limit their clinical utility, particu- advances in stimulation electrodes, in- peripheral nerves, infectious diseases larly in the elderly population. Hence, novations in implantable pulse gen- (e.g., herpes zoster, HIV, or leprosy), erators, and the introduction of novel metabolic disorders, cancer and its stimulation parameters have resulted in treatment, and injuries or diseases that a surge in the use of implantable thera- affect the central nervous system (e.g., pies. The relative safety and reversibil- stroke or spinal cord injury). Nearly a ity of this treatment modality, as well as fourth of people with chronic diabetes its cost-effectiveness over the long term, have neuropathic pain—a worldwide have made it an attractive strategy for estimate of nearly 50 million indi- managing patients with refractory, viduals. Moreover, neuropathic pain is experts are increasingly considering chronic neuropathic pain. Although reported to be more severe than non- interventional therapies such as nerve SCS has been used to treat a variety of neuropathic pain and can dramatically blocks and neuromodulatory strategies neuropathic pain states, controlled trials affect health-related quality of life. for patients with refractory neuropathic have shown the best evidence for long- pain and those who are intolerant to term efficacy in patients with failed back mendations for pharmacological systemic drugs. On the basis of the surgery syndrome (FBSS) and complex treatments have been published, available evidence from clinical trials, regional pain syndrome (CRPS) type I, including a recently updated NeuPSIG NeuPSIG published recommendations in and more recently in diabetic neuro- 2013 regarding the use of interventional pathic pain. Based on the GRADE cri- therapies for neuropathic pain. Sev- teria, a NeuPSIG consensus group rated eral more recent studies have provided the quality of evidence from clinical additional evidence for the role of trials as moderate, and gave it a “weak” neurostimulation therapies in the man- recommendation for use in FBSS with agement of neuropathic pain. This radiculopathy and CRPS.14 Although the issue of Pain: Clinical Updates reviews same report considered the evidence for the latest evidence for emerging neuro- the efficacy of SCS in diabetic neuro- stimulation therapies that may provide pathic pain to be low and labeled its 43 Several evidence-based recom- Srinivasa N. Raja, MD Department of Anesthesiology and Critical Care Medicine Johns Hopkins University Baltimore, Md., USA Email: [email protected] Mark Wallace, MD Department of Anesthesiology University of California San Diego, Calif., USA Email: [email protected] PAIN: CLINICAL UPDATES • SEPTEMBER 2015 14 13 1 recommendation as “inconclusive,” more and the number of positive versus recent controlled trials provide addi- negative electrodes used. The amplitude tional evidence for its efficacy. is the strength of the stimulation pulse. Stimulation Paradigms Measured in volts or milliamps, it is the primary control over the intensity of Conventional SCS that is associated with the sensation. Higher amplitudes will a paresthesia uses a monophasic, square- ultimately result in painful stimula- wave pulse at a frequency in the 40–80- tions. The highest amplitude that can be Hz range. In an attempt to improve suc- achieved with current devices is 15 V. cess and avoid some of the undesirable The pulse width is the amount of time side effects of SCS, some physicians are the stimulation pulse lasts and is mea- using new stimulation parameters, such sured in microseconds. Higher (wider) as burst and high-frequency SCS (Fig. 1). settings will cause the stimulation field Recent studies examining the long-term to “stay on” longer and depolarize both effectiveness of these strategies provide large- and small-diameter fibers. Lower encouraging observations that should be pulse width will narrow the stimula- confirmed by additional controlled trials. tion, resulting in mostly large-fiber Traditional SCS depolarization. Typical clinically used pulse widths range from 175 to 600 µs Whereas burst and high-frequency but can go as high as 1000 µs. Frequen- stimulation use fixed wave parameters, cy is the number of stimulation pulses traditional SCS adjusts the different pa- delivered per second. The frequency of rameters to achieve fiber depolarization traditional SCS can be as high as 1200 and paresthesias that overlap the pain- Hz. Increasing the frequency boosts the ful area. Parameters that can be adjust- number of action potentials generated ed include electrode polarity, amplitude, by the nerve. Changes in frequency pulse width, and frequency. Electrode produce a change in sensation from polarity controls the shape and density pulsing (low) to fluttering (high). Higher of the electrical field, as determined by frequencies dramatically affect battery the distance between the electrodes consumption. Burst SCS Burst stimulation consists of closely spaced, high-frequency stimuli delivered to the spinal cord (Fig. 1). The stimulus paradigm consists of a 40-Hz burst mode of constant-current stimuli with 5 spikes at 500 Hz per burst and pulse width and interspike intervals of 1 ms. A possible advantage of this stimulus paradigm is that it does not cause paresthesia in the painful region. In a randomized controlled trial (RCT), burst stimulation was able to improve back, limb, and general pain by 51%, 53%, and 55%, respectively, compared to 30%, 52%, and 31% with tonic stimulation. Similar significant improvements in pain now, least pain, and worst pain were observed with burst stimulation. The differences between tonic and burst stimulation could be due to more selective modulation of the medial pain pathways by burst stimulation, as evidenced by activation of the dorsal anterior cingulate cortex.9 More recent retrospective analysis of patients who were switched from tonic to burst stimulation suggests that the latter can rescue a proportion of those who Fig. 1. Spinal cord stimulation waveforms. 2 PAIN: CLINICAL UPDATES • SEPTEMBER 2015 paresthesia mapping is not necessary, thus shortening procedure time. A U.S. pilot study in 24 patients demonstrated a significant reduction in back and leg pain.42 A European study was conducted in 83 patients with primarily lowback pain. Seventy-two subjects had a successful trial. Long-term follow-up to 12 months showed a significant reduction in both back and leg pain. The study also reported significant improvements in the average Oswestry Disability Index score and in sleep disturbance, as well as high patient satisfaction.45 An ongoing clinical trial in the United States of subjects who have low back pain with or without lower-extremity pain is testing an SCS device that Fig. 2. Spinal cord stimulation (SCS) for diabetic neuropathic pain. (a) Average pain scores (VAS) for the SCS treatment group (dark gray) and control group (light gray) at baseline and after 1, 3, and 6 months of treatment; a high score corresponds with severe pain. (b) Average McGill Pain Questionnaire (MPQ) Quality of Life scores; a high score corresponds with severely disturbed daily activities and sleep. Error bars represent standard deviation. From de Vos et al.11 provides both traditional and high-frequency SCS (the ACCELERATE Trial). do not respond to tonic stimulation alternating-current sinusoidal Complex Regional Pain Syndrome and improve pain reduction in those waveform applied to a nerve results CRPS is a well-established indication for who do. Additional RCTs are needed in reversible block of activity. This SCS, for which it is approved by the U.S. to confirm these observations block occurs in three phases: an onset Food and Drug Administration (FDA). response, a period of asynchronous The primary evidence for effective- firing, and a steady state of complete ness of SCS in CRPS patients is based High-frequency stimulation uses fre- or partial block. This technology is on a prospective, randomized trial of quencies up to 10 kHz. Although the currently available in Europe and 54 patients followed for up to 5 years. currently available device is capable Australia and recently received ap- Kemler and coworkers20 randomized of amplitudes up to 15V and a pulse proval in the United States. Because of CRPS type I patients in a 2:1 ratio to two width up to 1000 ms, newer devices the high frequencies used, the device groups: SCS with physical therapy or reach 10 KHz with amplitudes of 1 requires a rechargeable battery to physical therapy alone. Two-thirds of to 5 mA and very low pulse width, support the high power consumption. the 24 patients in the SCS group were resulting in paresthesia-free stimula- It is used primarily to treat back pain implanted with devices after a success- tion. The exact mechanism of pain but has some effect on lower-extremi- ful trial stimulation. Pain was reduced relief is unclear, but preclinical studies ty pain. Leads are placed anatomically by 2.4 cm on a 10-cm visual analogue have shown that a high-frequency, over T9 in the midline; intraoperative scale (VAS) in the SCS group, whereas 8 High-Frequency Stimulation PAIN: CLINICAL UPDATES • SEPTEMBER 2013 1 3 it increased by 0.2 cm in the physical in pain. Among 45 patients available invasive treatment options, includ- therapy group. Moreover, 39% of SCS for evaluation approximately 3 years ing consideration of a trial of epidural patients, compared to 6% of control postoperatively, the authors reported steroid injections. patients, rated themselves as “much a successful outcome in 47% of SCS improved.” The observed beneficial patients versus 11.5% of the reoperation 48 patients, burst stimulation led to a effects in the SCS group persisted at 2 patients. The rate of crossover to alter- significant additional pain reduction years,22 but subsequent evaluations at native treatment was also significantly of approximately 28% in patients with 3–5-year follow-ups failed to demon- lower in the SCS patients (~20%) than FBSS, compared to that in patients strate differences in outcome between in the reoperation patients (>50%). who received conventional tonic 23 the groups. Despite a 42% reopera- In the second, larger RCT, 100 In a recent observational study of stimulation.10 tion rate in the SCS patients during the FBSS patients with more severe leg 5-year study, 95% of the patients who pain than back pain were randomized Painful Diabetic Neuropathy received SCS indicated that they would to conventional medical management Earlier small, prospective observational repeat the procedure. Other retrospec- (CMM) alone or CMM with SCS. The trials evaluating the effects of SCS on tive and prospective case series also primary outcome measure was the re- pain in patients with refractory painful have reported reduced pain, improved sponder rate (the proportion of patients diabetic neuropathy (PDN) reported function, and reduced medication use obtaining at least 50% relief of leg pain) substantial benefits, although the after SCS in CRPS patients. An indepen- at 6 months, after which patients were complication rate was 33% in one of the dent systematic review of the studies allowed to cross over. In the 88 patients trials.7,12 Two RCTs of SCS in patients concluded that SCS showed evidence for available for analysis, SCS was success- with PDN reported in 2014 provide ad- efficacy relative to conventional medical ful in 48% and 34% at 6 and 12 months, ditional evidence for the effectiveness management in patients with CRPS type respectively, in contrast to 9% and 7% of SCS in the management of PDN. In a I.38 Both NeuPSIG and the European in the CMM group. More than 50% of multicenter randomized trial, 36 PDN Federation of Neurological Societies subjects originally assigned to CMM patients with severe lower-limb pain (EFNS) gave a weak recommendation crossed over to receive SCS, whereas refractory to conventional therapy for use of SCS in CRPS type I, on the only 18% of SCS patients crossed over were randomized to receive either SCS basis of the moderate evidence.6,14 to CMM. Although the total health care in combination with the best medical cost in the SCS group was significantly treatment (SCS group, n = 22) or medi- higher, subjects in the SCS group expe- cal treatment alone (BMT group, n = Two published RCTs, along with several rienced significantly improved quality 14).39 Treatment success, determined long-term outcome case series, support of life and functional capacity, as well at 6 months, was defined as ≥50% pain the use of SCS for FBSS. Most studies as greater treatment satisfaction than relief or “(very) much improved” for evaluated the effects of SCS in patients those in the CMM group.31 Device- pain and sleep on the Patient Global who had treatment-refractory FBSS related reoperation is a concern, as 31% Impression of Change scale. with prominent radicular symptoms. In of the SCS patients available for follow- the first RCT, North et al. studied 50 up at 2 years had required surgical in 59% of patients in the SCS group patients who had undergone previous revision. Considering the strengths and compared to 7% in the BMT group. SCS spinal surgeries and were candidates limitations of these trials, the authors was not without risk in this population, for reoperation to alleviate chronic pain of a systematic review concluded that as one SCS patient died of a subdural that was more bothersome in their legs SCS appears to be more effective than hematoma. In a second, larger, multi- than their back. Patients were random- CMM and reoperation.38 Both NeuPSIG center controlled trial, 60 PDN patients ized to either treatment with SCS or and the EFNS gave SCS a weak recom- were similarly randomized in a 2:1 ratio reoperation, but they were allowed to mendation for FBSS.6,14 Because of the to receive best conventional medical cross over to the other treatment if dis- invasiveness of the procedure, the risk practice with (SCS group) or without satisfied with the results of their first of complications, and the relatively (control group) additional SCS therapy.11 treatment. The criterion for “success” low response rate to SCS, the NeuPSIG After 6 months of treatment, average was patient satisfaction with treat- recommendation was to reserve SCS pain scores decreased significantly ment and a 50% or greater reduction for patients who do not respond to less from 73 to 31 (0–100 VAS) in the SCS 21 Failed Back Surgery Syndrome 33 4 27 Treatment success was observed PAIN: CLINICAL UPDATES • SEPTEMBER 2015 group, but remained unchanged at 67 technique.48,49 PNS has been used for in the control group (Fig. 2). Improve- a variety of chronic neuropathic pain ments in quality of life measures were states, such as postsurgical neuralgias, also observed. In a recent observational post-traumatic neuralgia, occipital study that compared conventional neuralgia, and postherpetic neuralgia tonic stimulation with burst stimula- (for review see Petersen and Slavin ). tion, the latter led to a significant ad- PNS has also been used to alleviate a ditional 44% pain reduction on average variety of headaches, including chronic in patients with PDN.10 daily headaches, cluster headaches, and Other Neuropathic Pain States Editor-in-Chief 36 tion stump and phantom pains, posther- occipital nerve PNS for migraine failed petic neuralgia, spinal cord injury, and to meet its primary endpoint (difference other traumatic peripheral neuralgias. in responders, defined as patients who The evidence for effectiveness of SCS in achieved a ≥50% reduction in mean dai- these pain states has not been carefully ly VAS scores).37 However, the authors evaluated in controlled trials and is did find significant reductions in pain, based primarily on observational studies headache days, and migraine-related in small groups of subjects. disability. Peripheral nerve field stimulation in the region of maximal pain has also been used alone or in combina- The success of SCS for neuropathic pain tion with SCS, particularly for chronic may depend on appropriate patient axial low back pain.2,24 Although the selection. Psychological traits may play devices used for PNS are “off-label” in an important role in modeling individ- the United States, they are approved in ual differences in the pain experience. Europe for the treatment of intractable Hence, psychological screening might migraine and chronic low back pain. be useful in helping to predict which help physicians determine the sensory phenotype and the mechanism of pain in patients with neuropathic pain as well as their responses to SCS.3 Studies are needed to further explore whether strict patient selection based on psychological and sensory profiles can reduce the failure rate of SCS. Peripheral Nerve/Field Stimulation Dorsal Root Ganglion Stimulation Although traditional SCS has shown effectiveness in certain pain states, reports suggest that 30–40% of patients fail to achieve adequate pain relief or experience a reduction in effectiveness with time. Recently, the dorsal root ganglion (DRG) has emerged as a potential target for treating chronic neuropathic pain 26. Experts hypothesize that, relative to traditional SCS, stimulation of sensory neurons in the DRG may result in more precise and Peripheral nerve stimulation (PNS), selective stimulation, thereby reduc- first described nearly 50 years ago, has ing unwanted side effects observed recently become more attractive after with traditional SCS.25 Some authors the development of a percutaneous postulate that DRG stimulation may be PAIN: CLINICAL UPDATES • SEPTEMBER 2013 Pain Medicine, Palliative Medicine Australia Internal Medicine, Physiology Italy ized, double-blind, controlled trial of that quantitative sensory testing may Advisory Board Michael J. Cousins, MD, DSC Maria Adele Giamberardino, MD uncontrolled case series. A random- In addition, preliminary studies suggest Anesthesiology, Pain Medicine USA ies reporting benefits of PNS have been pathic pain states, such as post-amputa- patients are likely to benefit from SCS.4 Jane C. Ballantyne, MD, FRCA migraine, and to treat CRPS. Most stud- SCS is used to treat several other neuro- Predictors of Success Editorial Board Robert N. Jamison, PhD Psychology, Pain Assessment USA Patricia A. McGrath, PhD Psychology, Pediatric Pain Canada M.R. Rajagopal, MD Pain Medicine, Palliative Medicine India Maree T. Smith, PhD Pharmacology Australia Claudia Sommer, MD Neurology Germany Harriët M. Wittink, PhD, PT Physical Therapy The Netherlands Publishing Daniel J. Levin, Publications Director Elizabeth Endres, Consulting Editor Timely topics in pain research and treatment have been selected for publication, but the information provided and opinions expressed have not involved any verification of the findings, conclusions, and opinions by IASP. Thus, opinions expressed in Pain: Clinical Updates do not necessarily reflect those of IASP or of the Officers or Councilors. No responsibility is assumed by IASP for any injury and/or damage to persons or property as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends independent verification of diagnoses and drug dosages. © Copyright 2015 International Association for the Study of Pain. All rights reserved. For permission to reprint or translate this article, contact: International Association for the Study of Pain 1510 H Street NW, Suite 600, Washington, D.C. 20005-1020, USA Tel: +1-202-524-5300 Fax: +1-202-524-5301 Email: [email protected] www.iasp-pain.org 5 particularly beneficial when the pain distribution is in a region over which paresthesia is difficult to achieve with conventional SCS. (Fig. 3)29,30 In a multicenter, prospective, observational cohort study, 32 of 51 subjects with chronic neuropathic pain (63%) who completed a trial with a DRG-SCS device were implanted with permanent devices. Seven of those subjects had their device removed within a year, and the other 25 subjects were followed up to a year.30 The 56% pain reduction and 60% responder rate (>50% reduction in overall pain) reported by the authors are promising results, but they should be interpreted with caution owing to the uncontrolled nature of the study and the method of data analysis (not intention-to-treat). In addition, the safety of the procedure needs careful study, as 86 safety events were reported in 29 subjects, including temporary motor stimulation, cerebrospinal fluid leak and associated headache, infection, and lead revisions. Similar beneficial Fig. 3. Lead placement for dorsal root ganglion stimulation. results were observed in a group of subjects with lower-extremity CRPS or CRPS. The study’s results, which will motor cortex stimulation during the (8 of 11 trialed subjects received device include safety and efficacy endpoints first few months, the pain relief may implants) who were followed for a year. and responder rate analysis, may help to wane over longer periods of time.17,40 Several recent abstracts presented at determine the efficacy of DRG stimula- the North American Neuromodulation tion in this population. 46 Noninvasive brain stimulation techniques include repetitive tran- Society also suggest promising benefits of scranial magnetic stimulation (rTMS), transcranial direct current stimula- investigation. Huygen et al. reported Motor Cortex and Noninvasive Brain Stimulation pooled data from prospective studies in Motor cortex stimulation is based on ance noninvasive cortical stimula- Europe of 19 patients with upper-limb an observation nearly 25 years ago tion (RINCE; for recent reviews, see neuropathic pain of various etiologies by Tsubokawa et al.44 that stimulation O’Connell et al.35 and Young et al.50). and showed mean reductions in pain of the precentral gyrus below motor In contrast to conventional electrical of 54.6% and 58.6% at 3 and 6 months, threshold relieves pain in patients with stimulation that is likely to reach only respectively, with concurrent improve- thalamic pain. A number of subsequent the most superficial layers of the cortex, ments in quality of life. clinical observations have shown ef- the magnetic field created by rTMS DRG stimulation in mixed neuropathic pain states that are worthy of further 18 Recently, 152 patients were enrolled tion (tDCS), cranial electrotherapy stimulation (CES), and reduced imped- ficacy in trigeminal neuropathic pain passes through the scalp and cranium in a prospective, randomized, multi- and deafferentation syndromes such as to excite or inhibit various cortical and center, controlled trial (ACCURATE poststroke pain and pain resulting from subcortical neural networks. Similar Trial) designed to evaluate the safety spinal cord injury or brachial plexus in- to other neuromodulation techniques, and efficacy of a DRG stimulation device juries (for reviews see Sukul and Slavin the effects of rTMS may depend on the for treatment of chronic lower-limb and Moore et al.32). Although more than positioning of the coil and its orientation pain caused by nerve injuries (causalgia) 50% of patients appear to respond to to the underlying brain structures, the 6 41 PAIN: CLINICAL UPDATES • SEPTEMBER 2015 its role as a therapeutic alternative (see stimulation parameters, and the dura- refractory neuropathic pain syndromes. tion of stimulation. Reviewers postulate 50 that high-frequency (>5 Hz) stimulation concluded that “there is a sufficient leads to increased cortical excitability body of evidence to accept with level A Conclusions and a reduction in cortical inhibition, (definite efficacy) the analgesic effect of The clinical literature now spans more whereas low-frequency stimulation high-frequency (HF) rTMS of the pri- than three decades on the clinical (≤1 Hz) causes a transient reduction in mary motor cortex (M1) contralateral to use of spinal cord stimulation to treat cortical excitability without affecting the pain.”28 Relative contraindications of chronic neuropathic pain. Although cortical inhibition.16 Although several TMS include a history of epilepsy and the evidence is “weak” on the efficacy reports of uncontrolled trials suggest the presence of aneurysm clips, deep of this important therapy, this does not that rTMS of the motor cortex (M1) brain electrodes, and cochlear implants. imply that it is not an effective therapy. A recent evidence-based guideline has beneficial effects in various central review by Keifer et al.19 for details). The “weak” evidence is not the result of and peripheral neuropathic pain states, Deep Brain Stimulation results of controlled trials have been Deep brain stimulation (DBS) is an difficulties in successfully conducting mixed. A recently updated Cochrane accepted treatment for disorders like controlled clinical trials with interven- review35 included 56 trials (1710 ran- Parkinson’s disease that are associ- tional therapies.34 This problem stresses domized subjects): 30 studies of rTMS, ated with motor signs such as rigidity, the need for alternative methods such 11 of CES, 14 of tDCS, and one study bradykinesis, and tremor. The use of as large registries to study the indi- of RINCE. Several studies included a chronic intracranial stimulation for cations and clinical benefits of this mixture of central, peripheral, and fa- pain, however, remains controversial. important therapy. Nonetheless, more cial neuropathic pain states of various Various DBS sites, including the inter- recent, well-conducted studies support etiologies. The authors concluded that nal capsule, various nuclei in the sen- both the efficacy and cost-effectiveness single doses of high-frequency rTMS of sory thalamus, the periaqueductal and of this therapy in several neuropathic the motor cortex may have small short- periventricular gray, the motor cortex, pain syndromes. term effects on chronic pain (12%; 95% CI, septum, nucleus accumbens, posterior 8–15%). In addition, multiple-dose studies hypothalamus, and anterior cingulate field of stimulation over the past three failed to consistently demonstrate effec- cortex, have been examined as poten- decades, improvements in SCS technol- tiveness, and low-frequency rTMS, rTMS tial brain targets for pain control. The ogy as well as new stimulation thera- applied to the prefrontal cortex, CES, and effectiveness of DBS has been the sub- pies are emerging that should prove to tDCS were ineffective in the treatment of ject of case series in diverse etiologies be an important addition to our stimu- chronic pain. The primary advantage of of chronic pain, but results have been lation armamentarium. These new these techniques is their excellent safety inconsistent. Two multicenter trials therapies are not likely to replace SCS, profile, but the evidence for efficacy is in- of DBS for chronic pain conducted in but rather will supplement it or treat conclusive and the magnitude of benefi- the 1990s failed to demonstrate long- patients not responsive to traditional cial effects failed to meet the threshold of term beneficial effects.5 Thus, current SCS. By expanding the horizon of stim- minimal clinical significance (≥15%) in the evidence is inconclusive for determin- ulation techniques, we will continue to systematic review. Some have suggested ing the role of DBS in the treatment of successfully treat an increasing propor- that rTMS can be used as a complemen- neuropathic pain. Ongoing, better-con- tion of neuropathic pain patients who tary therapy in patients with chronic trolled trials may shed more light on currently have limited options. References 1. Bhadra N, Kilgore KL. High-frequency electrical conduction block of mammalian peripheral motor nerve. Muscle Nerve 2005;32:782–90. 2. Bernstein CA, Paicius RM, Barkow SH, Lempert-Cohen C. Spinal cord stimulation in conjunction with peripheral nerve field stimulation for the treatment of low back and leg pain: a case series. Neuromodulation 2008;11:116–23. 3. Campbell CM, Buenaver LF, Raja SN, Kiley KB, Swedberg LJ, Wacnik PW, Cohen SP, Erdek MA, Williams KA, Christo PJ. 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