简介
脊髓电刺激（SCS）的诞生归功于Wall和Melzack在1965年里程碑式的论文中提出的门控制理论（GCT）的概念，该理论提出“可以通过选择性激活大而快速的传导纤维来控制疼痛”。2年后，首次报道了背柱刺激的临床应用，此后该领域逐渐扩大。
尽管SCS技术在过去几十年中有了很大的发展，但在过去几年中，出现了几种新型设备和刺激模式，包括高频技术、背根神经节（DRG）刺激、burst刺激、和其他模式。一些新波形，如高频刺激，挑战了我们在GCT框架内阐明其作用机制的能力。
从根本上讲，SCS无论是哪种类型，都涉及到硬膜外腔金属触点之间电场的产生。外加电场根据电极附近组织的性质改变跨膜电位，如硬脑膜、脑脊液层和白质。对于可兴奋膜，例如在附近的背柱轴突中发现的膜，电场可以触发一个或多个动作电位，这取决于轴突的生物电特性（直径、髓鞘状态和电阈值）。由于电极通常放置在背柱的生理中线附近（DRG刺激的情况除外），电刺激会激活背柱轴突，导致动作电位的顺向和逆向传递，从而产生节段和脊髓上效应（图1）。大直径轴突的动作电位阈值较低，因此优先于较小的纤维被激活。
图片来源于网络
常规SCS优先激活大的Ap背柱轴突。这种激活可以测量为在周围神经中逆向传播的动作电位，为硬膜外动作电位，为头皮上记录的体感诱发电位，为肢体和躯干肌肉的肌肉抽搐，为患者感觉到的感觉异常。除了激发动作电位外，电刺激还会改变暴露在电场中的神经元和其他类型细胞的膜电位，从而改变受影响节段的电化学特性。
电荷可以通过各种波形转移，净效应取决于波形特征。产生的波形可以根据脉冲幅度、宽度和频率进行表征，这些结合起来可以向组织输送一定量的电荷。据信，释放的电荷量对产生的电场和随后的神经募集至关重要。随着设备电子技术的进步，用特定波形和各种阴极/阳极组合精确传递电脉冲的能力呈指数级增长。传统刺激、突发刺激和高频刺激因频率、波形模式和电荷转移的平衡方式而异（图2），因此产生不同的轴突和相邻神经组织激活模式。脉冲群在处理电荷平衡方面是独特的：五个单独恒流脉冲的脉冲群在脉冲群结束时电荷平衡，而不是每个尖峰（图2）。关于SCS激活哪些纤维，以及不同波形和粘度下纤维激活如何变化，存在着重要的争论。此外，尚不清楚需要激活哪些特定纤维以达到最佳疼痛缓解，以及慢性SCS中激活模式如何改变。
常规波形
临床效果
FBSS是一种常见的疾病，定义为支架周围疼痛或手术治疗后的复发性疼痛，在腰椎手术后10%至40%的患者中存在。这种情况被认为是由神经性背部和腿部疼痛引起的，与高痛苦程度、功能下降、高失业率和医疗费用上升有关。这一临床实体缺乏良好的治疗选择，许多已发表的报告描述了这一人群中SCS的研究（表1）。
图片来源于网络
许多早期病例系列和前瞻性研究表明，SCS对该患者群体有益。North等人进行了随机对照试验（RCT），比较了传统SCS和重复腰椎手术。在随机分为SCS组和再次手术组的60名患者中，SCS组的疼痛缓解率和患者满意度明显高于再次手术组50%或更高。该报告明确证实，对于FBSS，对于符合手术干预标准的患者，SCS优于再次手术。在另一个经典的随机对照试验中，Kumar等人比较了保守医疗管理（CMM）和SCS在该患者群体中的作用（48名CMM，52名SCS患者），并测量了6个月、12个月和24个月时的结果。SCS在腿痛的所有时间点均优于CMM(≥减少50%）、功能和健康相关的生活质量。在迄今为止最大的一项随机对照试验中，对218名患者的最佳医疗管理（OMM）与OMM+SCS进行了比较。42名患者已完成试验，尽管完整报告尚未发表，但初步报告表明，SCS组的患者比例明显高于单纯OMM组。达到了主要结果，定义为：≥6个月时，腰痛强度降低50%。
传统SCS被证明优于物理疗法治疗复杂性区域疼痛综合征，Kemler等人的一项研究中，作者报告了一个平均值。在意向治疗分析中，6个月时的疼痛在视觉模拟量表（VAS）上减少2.4 cm，而实际使用SCS治疗的疼痛在视觉模拟量表（VAS）上减少3.6 cm。对照组的疼痛评分组在6个月时增加了0.2厘米。随访5年发现疼痛缓解接受SCS治疗的患者逐渐减少，因为VAS平均得分为2.5 cm与基线检查时相比减少了3.6 cm（相比之下，6个月时减少了3.6 cm）。相比之下接受物理治疗的对照组在5年后显示出1厘米的下降（p=0.06）。在两项前瞻性随机对照试验中，对疼痛性糖尿病周围神经病变患者的常规SCS与药物治疗进行了比较。这些研究证明了其优越性SCS组中约60%的患者，但对照组只有5-7%的患者在6个月时达到了成功标准。SCS组的结果随着时间的推移而持续，80%的患者使用他们的设备和55%的患者在5年内取得治疗成功。
人体机制研究
背柱纤维的激活是否会导致感觉阈值和痛阈的客观测量发生变化？由于患者在使用常规SCS时出现感觉异常，这表明传入通路被紧张性激活，因此可以预测感觉阈值的变化。早期的一份关于刺激背柱治疗疼痛的报告指出，触觉和振动感觉没有变化，但皮肤刺激的痛阈增加（表2）。一些研究检测到SCS接触和振动阈值的变化，而其他研究则没有。同样，在一项研究中，SCS改变了机械性痛阈，而在其他研究中，SCS没有改变机械性痛阈。在一项针对CRPS患者的大型研究中，SCS患者与对照组之间的温度检测阈值没有差异，仅检测到对机械性痛觉过敏的轻微影响。一些人观察到了温度辨别力的变化，对疼痛的强直性热刺激的时间总和，和热痛，而其他人没有。与接受短期刺激的患者相比，长期植入患者对电刺激的检测阈值和痛阈分别增加了。在最终进行植入的试验患者中，SCS显示出增加对电刺激的疼痛耐受阈值，但在无反应的试验患者中没有。有趣的是，与关闭设备时相比，长期植入患者在设备打开时的电流感知阈值增加，这突出了测试时间的重要性。最近进行的一项小型但仔细的研究在SCS试验前和植入后3个月内对成功试验的患者进行纵向跟踪，并检查了一系列实验室疼痛测量，包括中枢致敏和疼痛下降调节。作者发现，除了接受SCS治疗的患者的热-时间总和减少外，随时间的推移没有差异。很难从上述积累的证据中得出明确结论，这可能反映了不同的实验方式，如受试者人数少、不同的疼痛病因（和相关的神经损伤）、不同的SCS导联位置（硬膜外与硬膜下）和刺激频率、急性与慢性刺激状态等。总的来说，可以假设，尽管背柱受到强直性激活，但常规SCS在很大程度上不会影响感觉阈值和痛阈，在控制急性疼痛方面的作用微乎其微。
图片来源于网络
SCS对伤害性信息的高阶处理有影响和皮质水平。直接在人体内确定节段效应具有挑战性；然而，对脊髓反射的影响可以从神经生理学测试中推断出来（表3）。对于例如，发现SCS抑制患者的感觉运动反射，如H反射FBSS引起的下肢疼痛。这种抑制被认为至少部分发生通过对运动神经元的直接影响，尽管脊髓的调节更为复杂可能存在感觉运动回路。SCS对电机系统的影响是稳健的可靠，SCS已用于治疗痉挛和改善患者的运动功能脊髓损伤和其他运动障碍，如多发性硬化症和帕金森氏病。伤害性感觉运动反射（RIII）是一种多突触脊髓反射被认为是伤害感受的一种客观生理测量，并且已经被证明与感知到的疼痛呈正相关。在神经病理性疼痛患者的两项研究中，SCS显示出抑制RIII并与刺激效果相关。RIII反射是一种很有希望的测试，可用于确定最佳刺激参数，并作为治疗效果的客观评价。
图片来源于网络
除节段效应外，SCS还调节皮层对体感信息的处理，对此进行了综述。SCS已被证明可降低皮层兴奋性，如通过感觉诱发电位（SEP）测量，可使病理正常化皮质活动。这些措施可能有助于预测疼痛缓解。与其他SEP变化并不总是与临床成功相关，这意味着患者SEP显著抑制时，有时疼痛缓解程度很小。因此，更大需要进行研究以确定SEP是否可用于预测结果。
慢性疼痛状态下大脑活动发生病理改变，和大量证据支持皮质淋巴结构中的异常活动是慢性疼痛。令人信服的假设是，SCS通过抑制和使病理性皮质连接正常化，减少皮质淋巴激活。许多研究已经通过成像研究了SCS是如何改变皮质处理的方法，如功能磁共振成像、PET、SPECT和133氙气吸入。期间的皮质变化脊髓干细胞可能表现为背柱刺激或痛觉抑制的直接效应信号来自外围，或者它们可能反映对躯体感觉和情感处理。最早的研究表明使用刺激器的患者的功能磁共振成像的可行性，发现在三名使用临时电极的患者中，感觉和扣带回皮质的激活增加。人发现SCS减少丘脑到扣带回的连接，初级运动和躯体感觉皮层，和调节静息状态连通性。SCS可增加局部脑血流量（CBF），尤其是在颈部刺激时，表明对CBF监管中心有直接影响。使用PET和SPECT的研究CBF成像也有类似的发现，多个大脑的活动正常化区域，包括丘脑、中央后回、眶额皮质和前扣带回皮质在一项研究中。在丘脑、前扣带回发现局部CBF改变皮质、前额叶和双侧顶叶联合区。最新的SCS系统MRI兼容，可以提供无感觉异常的刺激，允许使用安慰剂对照组，现在可以设计相关研究来描绘皮质结构持续SCS镇痛。未来的研究工作应解决基本问题例如，是否可以通过患者的基线成像预测长期SCS成功，例如，使用静息状态功能磁共振成像。其他研究可能涉及成像是否可以用于调整疼痛缓解不佳患者的刺激参数。
临床前研究
令人信服的证据表明，传统SCS介导通过结合节段和脊髓上机制，通过逆转慢性疼痛状态下发现的神经元过度活跃和适应不良变化（表4）。早期报道表明，SCS介导的镇痛可以通过阻断抑制来阻断和SCS导致抑制性神经递质释放增加由GCT提供。鞘内注射GABA B受体激动剂巴氯芬，增强大鼠的SCS镇痛作用和解救无反应者，在临床上，可提高SCS对反应不良的神经病理性疼痛患者的疗效。
图片来源于网络
SCS调节其他神经递质，包括胆碱能、5-羟色胺能和阿片能系统。SCS可增加有反应大鼠的乙酰胆碱水平，但无反应动物的乙酰胆碱水平不增加，M4毒蕈碱受体的激活可增强SCS介导的镇痛作用。与巴氯芬类似，可乐定是一种α-2肾上腺素受体激动剂，可增加背角乙酰胆碱的释放，在大鼠鞘内给药时可增强SCS的镇痛不足，并在一项小型临床试验中为患者提供持续的长期益处。除了乙酰胆碱外，SCS还诱导脑内5-羟色胺的释放猫和老鼠的背角。5-羟色胺受体5-HT（2A）和5HT（4）拮抗剂阻断了SCS的镇痛作用，而鞘内注射5-HT（3）激动剂增强了SCS的镇痛作用。在大鼠神经病理性疼痛模型中，这种作用被GABA B受体的抑制所阻断。最近一项在低（4 Hz）和典型（60 Hz）频率下使用延长SCS的研究发现，阿片受体亚型存在差异调节，因此纳洛酮阻断μ阿片受体可阻止SCS介导的低频镇痛，而纳曲多尔阻断δ阿片受体可阻断60 Hz刺激的效应。有趣的是，同一组发表了一项研究，其中丙谷胺（一种增强类阿片镇痛特性的药物）对大鼠SCS镇痛或体力活动水平没有影响。另一组发现，阿片类拮抗剂纳洛酮可阻断早期SCS（神经损伤后3天给予），但对晚期SCS无影响。
SCS抑制宽动态范围（WDR）神经元（一类输出神经元）的活性位于背角深层。这一事实是相关的，因为WDR神经元GCT传输细胞的候选细胞，对脊髓疼痛的处理和神经病理性疼痛的发展。SCS介导的WDR神经元抑制可以通过上述神经递质系统的调节来实现，尽管缺乏电路级的理解。最近，SCS（用于刺激Aβ纤维）被证明会导致大脑中兴奋性突触传递的长期抑制浅背角（第二层）。这种突触抑制在这两种细胞中都被观察到兴奋性和抑制性神经元；然而，网络层面的影响仍然未知。这个大麻素受体1型（CB1）拮抗剂可阻断突触抑制，将SCS镇痛机制与成熟的疼痛控制系统联系起来。最近的两项研究表明，鞘内输注CB1受体拮抗剂AM251，阻断SCS介导的神经源性疼痛大鼠机械性痛觉过敏的逆转。
上述对WDR神经元的研究并未证实所研究的神经元为投射神经元。最近的一项研究通过专门记录来自投射神经元的伤害感受特异性和WDR亚型。作者观察到对不同频率的20秒长SCS序列的异质响应，支持用复杂的微电路可以更好地解释SCS的影响而不是通过门控机制进行交互。
由于SCS通过顺向背柱动作电位传递引起脊髓上区域的激活，因此最近的研究试图梳理出可归因于脊髓上回路的镇痛比例以及所涉及的神经递质。在患有慢性背柱损伤的大鼠中，当在病变的头侧或尾侧水平应用SCS时，SCS在缓解疼痛方面同样有效，每个部位产生的疼痛缓解量约为完整大鼠疼痛缓解量的50%。腹腔注射GABA（A和B）、5-羟色胺、β和α肾上腺素能受体以及多巴胺能受体的拮抗剂，可不同程度地抑制触觉和热超敏反应，表明节段和脊髓上激活涉及不同的回路和神经递质。脊髓干细胞的脊髓上效应可能是由头侧腹髓质介导的，这是一个关键的大脑区域，对伤害感受的下行调节至关重要，正如Song等人最近所显示的，他们报告说，反应大鼠的脊髓干细胞导致抗伤害感受性OFF和5-羟色胺能样神经元的自发活动增加。其他脊髓上环路可能包括肾上腺素能神经元，尽管确切机制尚不清楚。
文章来源：AD Sdrulla, Y Guan, and SN Raja“Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanism” Pain Pract. 2018 November ; 18(8): 1048–1067. doi:10.1111/papr.12692.
参考文献：
1. Melzack R, Wall PD. Pain mechanisms: a new theory. Science (New York, N.Y.). 1965;150:971– 979.
2. Smits H, van Kleef M, Holsheimer J, Joosten EA. Experimental spinal cord stimulation and neuropathic pain: mechanism of action, technical aspects, and effectiveness. Pain Pract. 2013;13:154–168. [PubMed: 22780956]
3. De Ridder D, Vanneste S, Plazier M, van der Loo E, Menovsky T. Burst spinal cord stimulation: toward paresthesia-free pain suppression. Neurosurgery. 2010;66:986–990. [PubMed: 20404705]
4. Spinal Cord Stimulation. Available at: http://www.aans.org/Patients/Neurosurgical-Conditions-andTreatments/Spinal-Cord-Stimulation (accessed 9/18/2017).
5. Shealy CN, Mortimer JT, Reswick JB. Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesth Analg. 1967;46:489–491. [PubMed: 4952225]
6. van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155:654–662. [PubMed: 24291734]
7. Thomson S Failed back surgery syndrome - definition, epidemiology and demographics. Br J Pain. 2013;7:56–59. [PubMed: 26516498]
8. Grider JS, Manchikanti L, Carayannopoulos A, Sharma ML, Balog CC, Harned ME, et al. Effectiveness of spinal cord stimulation in chronic spinal pain: a systematic review. Pain Physician. 2016;19:E33–54. [PubMed: 26752493]
9. Deer TR, Krames E, Mekhail N, Pope J, Leong M, Stanton-Hicks M, et al. The appropriate use of neurostimulation: new and evolving neurostimulation therapies and applicable treatment for chronic Sdrulla et al. Page 13 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript pain and selected disease states. Neuromodulation. 2014;17:599–615; discussion 615. [PubMed: 25112892]
10. Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, et al. Novel 10-kHz highfrequency therapy (HF10 therapy) is superior to traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: the SENZA-RCT randomized controlled trial. Anesthesiology. 2015; 123:851–860. [PubMed: 26218762]
11. Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, et al. Comparison of 10- kHz high-frequency and traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: 24-month results from a multicenter, randomized, controlled pivotal trial. Neurosurgery. 2016;79:667–677. [PubMed: 27584814]
12. Deer TR, Levy RM, Kramer J, Poree L, Amirdelfan K, Grigsby E, 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. Pain. 2017;158:669–681. [PubMed: 28030470]
13. De Ridder D, Plazier M, Kamerling N, Menovsky T, Vanneste S. Burst spinal cord stimulation for limb and back pain. World Neurosurg. 2013;80:642–649.e641. [PubMed: 23321375]
14. Miller JP, Eldabe S, Buchser E, Johanek LM, Guan Y, Linderoth B. Parameters of spinal cord stimulation and their role in electrical charge delivery: a review. Neuromodulation. 2016;19:373– 384. [PubMed: 27150431]
15. Veizi E, Hayek SM, North J, Brent Chafin T, Yearwood TL, Raso L, et al. Spinal cord stimulation (SCS) with anatomically guided (3D) neural targeting shows superior chronic axial low back pain relief compared to traditional SCS-LUMINA study. Pain Med. 2017;18:1534–1548. [PubMed: 28108641]
16. Sun FT, Morrell MJ. Closed-loop neurostimulation: the clinical experience. Neurotherapeutics. 2014; 11:553–563. [PubMed: 24850309]
17. Linderoth B, Foreman RD. Conventional and Novel Spinal Stimulation Algorithms: Hypothetical Mechanisms of Action and Comments on Outcomes. Neuromodulation. 2017;20:525–533. [PubMed: 28568898]
18. Oakley JC, Prager JP. Spinal cord stimulation: mechanisms of action. Spine (Phila Pa 1976). 2002;27:2574–2583. [PubMed: 12435996]
19. Meyerson BA, Linderoth B. Mechanisms of spinal cord stimulation in neuropathic pain. Neurol Res. 2000;22:285–292. [PubMed: 10769822]
20. Parker JL, Karantonis DM, Single PS, Obradovic M, Cousins MJ. Compound action potentials recorded in the human spinal cord during neurostimulation for pain relief. Pain. 2012;153:593– 601. [PubMed: 22188868]
21. Holsheimer J, Buitenweg JR. Review: Bioelectrical mechanisms in spinal cord stimulation. Neuromodulation. 2015;18:161–170; discussion 170. [PubMed: 25832787]
22. Barolat G Epidural spinal cord stimulation: anatomical and electrical properties of the intraspinal structures relevant to spinal cord stimulation and clinical correlations. Neuromodulation. 1998;1:63–71. [PubMed: 22150938]
23. Hunter JP, Ashby P. Segmental effects of epidural spinal cord stimulation in humans. J Physiol. 1994;474:407–419. [PubMed: 8014902]
24. Buonocore M, Bonezzi C, Barolat G. Neurophysiological evidence of antidromic activation of large myelinated fibres in lower limbs during spinal cord stimulation. Spine (Phila Pa 1976). 2008;33:E90–93. [PubMed: 18277861]
25. Machida M, Weinstein SL, Yamada T, Kimura J. Spinal cord monitoring. Electrophysiological measures of sensory and motor function during spinal surgery. Spine (Phila Pa 1976). 1985;10:407–413. [PubMed: 4049106]
26. Tsuyama N, Tsuzuki N, Kurokawa T, Imai T. Clinical application of spinal cord action potential measurement. Int Orthop. 1978;2:39–46.
27. Halter J, Dolenc V, Dimitrijevic MR, Sharkey PC. Neurophysiological assessment of electrode placement in the spinal cord. Appl Neurophysiol. 1983;46:124–128. [PubMed: 6322684]
28. Dimitrijevic MR, Faganel J, Sharkey PC, Sherwood AM. Study of sensation and muscle twitch responses to spinal cord stimulation. Int Rehabil Med. 1980;2:76–81. [PubMed: 6969709] Sdrulla et al. Page 14 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
29. Barolat G, Massaro F, He J, Zeme S, Ketcik B. Mapping of sensory responses to epidural stimulation of the intraspinal neural structures in man. J Neurosurg. 1993;78:233–239. [PubMed: 8421206]
30. Vallejo R, Bradley K, Kapural L. Spinal cord stimulation in chronic pain: mode of action. Spine (Phila Pa 1976). 2017;42 Suppl 14:S53–S60. [PubMed: 28368982]
31. Holsheimer J Computer modelling of spinal cord stimulation and its contribution to therapeutic efficacy. Spinal Cord. 1998;36:531–540. [PubMed: 9713921]
32. Coburn B Electrical stimulation of the spinal cord: two-dimensional finite element analysis with particular reference to epidural electrodes. Med Biol Eng Comput. 1980; 18:573–584. [PubMed: 7464280]
33. Sin WK, Coburn B. Electrical stimulation of the spinal cord: a further analysis relating to anatomical factors and tissue properties. Med Biol Eng Comput. 1983;21:264–269. [PubMed: 6876898]
34. Holsheimer J Which neuronal elements are activated directly by spinal cord stimulation. Neuromodulation. 2002;5:25–31. [PubMed: 22151778]
35. Zucco F, Ciampichini R, Lavano A, Costantini A, De Rose M, Poli P, et al. Cost- effectiveness and cost-utility analysis of spinal cord stimulation in patients with failed back surgery syndrome: results from the PRECISE study. Neuromodulation. 2015;18:266–276; discussion 276. [PubMed: 25879722]
36. Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, et al. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome. Pain. 2007; 132:179–188. [PubMed: 17845835]
37. Taylor RS, Desai MJ, Rigoard P, Taylor RJ. Predictors of pain relief following spinal cord stimulation in chronic back and leg pain and failed back surgery syndrome: a systematic review and meta-regression analysis. Pain Pract. 2014;14:489–505. [PubMed: 23834386]
38. Cho JH, Lee JH, Song KS, Hong JY, Joo YS, Lee DH, et al. Treatment outcomes for patients with failed back surgery. Pain Physician. 2017;20:E29–e43. [PubMed: 28072795]
39. Baber Z, Erdek MA. Failed back surgery syndrome: current perspectives. J Pain Res. 2016;9:979– 987. [PubMed: 27853391]
40. North RB, Kidd DH, Farrokhi F, Piantadosi SA. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial. Neurosurgery. 2005;56:98–106; discussion 106–107.
41. Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, et al. The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery. 2008;63:762–770; discussion 770. [PubMed: 18981888]
42. Rigoard P, Desai MJ, North RB, Taylor RS, Annemans L, Greening C, et al. Spinal cord stimulation for predominant low back pain in failed back surgery syndrome: study protocol for an international multicenter randomized controlled trial (PROMISE study). Trials. 2013;14:376. [PubMed: 24195916]
43. National Library of Medicine. Spinal Cord Stimulation for Predominant Low Back Pain. Available at: https://ClinicalTrials.gov/show/NCT01697358 (accessed 9/18/2017).
44. Turner JA, Hollingworth W, Comstock BA, Deyo RA. Spinal cord stimulation for failed back surgery syndrome: outcomes in a workers’ compensation setting. Pain. 2010;148:14–25. [PubMed: 19875232]
45. Kemler MA, Barendse GA, van Kleef M, de Vet HC, Rijks CP, Furnee CA, et al. Spinal cord stimulation in patients with chronic reflex sympathetic dystrophy. N Engl J Med. 2000;343:618– 624. [PubMed: 10965008]
46. Kemler MA, de Vet HC, Barendse GA, van den Wildenberg FA, van Kleef M. Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: five-year final follow- up of patients in a randomized controlled trial. J Neurosurg. 2008;108:292–298. [PubMed: 18240925]
47. de Vos CC, Meier K, Zaalberg PB, Nijhuis HJ, Duyvendak W, Vesper J, et al. Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial. Pain. 2014;155:2426–2431. [PubMed: 25180016] Sdrulla et al. Page 15 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
48. Slangen R, Schaper NC, Faber CG, Joosten EA, Dirksen CD, van Dongen RT, et al. Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective two-center randomized controlled trial. Diabetes Care. 2014;37:3016–3024. [PubMed: 25216508]
49. van Beek M, Slangen R, Schaper NC, Faber CG, Joosten EA, Dirksen CD, et al. Sustained treatment effect of spinal cord stimulation in painful diabetic peripheral neuropathy: 24-month follow-up of a prospective two-center randomized controlled trial. Diabetes Care. 2015;38:e132– 134. [PubMed: 26116722]
50. van Beek M, Geurts JW, Slangen R, Schaper NC, Faber CG, Joosten EA, et al. Severity of neuropathy is associated with long-term spinal cord stimulation outcome in painful diabetic peripheral neuropathy: five-year follow-up of a prospective two-center clinical trial. Diabetes Care. 2017.
51. Deer T, Slavin KV, Amirdelfan K, North RB, Burton AW, Yearwood TL, et al. Success Using Neuromodulation With BURST (SUNBURST) study: results from a prospective, randomized controlled trial using a novel burst waveform. Neuromodulation. 2017.
52. Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for chronic back and leg pain and failed back surgery syndrome: a systematic review and analysis of prognostic factors. Spine. 2005;30:152–160. [PubMed: 15626996]
53. Shealy CN, Mortimer JT, Hagfors NR. Dorsal column electroanalgesia. J Neurosurg. 1970;32:560– 564. [PubMed: 5438096]
54. Lindblom U, Meyerson BA. Influence on touch, vibration and cutaneous pain of dorsal column stimulation in man. Pain. 1975;1:257–270. [PubMed: 1088447]
55. Eisenberg E, Backonja MM, Fillingim RB, Pud D, Hord DE, King GW, et al. Quantitative sensory testing for spinal cord stimulation in patients with chronic neuropathic pain. Pain Pract. 2006;6:161–165. [PubMed: 17147592]
56. Nashold BS, Jr., Friedman H Dorsal column stimulation for control of pain. Preliminary report on 30 patients. J Neurosurg. 1972;36:590–597. [PubMed: 5026545]
57. Meier K, Nikolajsen L, Sorensen JC, Jensen TS. Effect of spinal cord stimulation on sensory characteristics: a randomized, blinded crossover study. Clin J Pain. 2015;31:384–392. [PubMed: 25119512]
58. Larson SJ, Sances A, Jr., Riegel DH, Meyer GA, Dallmann DE, Swiontek T Neurophysiological effects of dorsal column stimulation in man and monkey. J Neurosurg. 1974;41:217–223. [PubMed: 4210432]
59. Rasche D, Ruppolt MA, Kress B, Unterberg A, Tronnier VM. Quantitative sensory testing in patients with chronic unilateral radicular neuropathic pain and active spinal cord stimulation. Neuromodulation. 2006;9:239–247. [PubMed: 22151713]
60. Campbell CM, Buenaver LF, Raja SN, Kiley KB, Swedberg LJ, Wacnik PW, et al. Dynamic pain phenotypes are associated with spinal cord stimulation-induced reduction in pain: a repeated measures observational pilot study. Pain Med. 2015;16:1349–1360. [PubMed: 25800088]
61. Kemler MA, Reulen JP, Barendse GA, van Kleef M, de Vet HC, van den Wildenberg FA. Impact of spinal cord stimulation on sensory characteristics in complex regional pain syndrome type I: a randomized trial. Anesthesiology. 2001;95:72–80. [PubMed: 11465587]
62. Ahmed SU, Zhang Y, Chen L, St Hillary K, Cohen A, Vo T, et al. Effects of spinal cord stimulation on pain thresholds and sensory perceptions in chronic pain patients. Neuromodulation. 2015;18:355–360. [PubMed: 26033205]
63. Marchand S, Bushnell MC, Molina-Negro P, Martinez SN, Duncan GH. The effects of dorsal column stimulation on measures of clinical and experimental pain in man. Pain. 1991;45:249–257. [PubMed: 1876434]
64. Eisenberg E, Burstein Y, Suzan E, Treister R, Aviram J. Spinal cord stimulation attenuates temporal summation in patients with neuropathic pain. Pain. 2015;156:381–385. [PubMed: 25599230]
65. Doerr M, Krainick JU, Thoden U. Pain perception in man after long term spinal cord stimulation. J Neurol. 1978;217:261–270. [PubMed: 75962]
66. Mironer YE, Somerville JJ. Pain tolerance threshold: a pilot study of an objective measurement of spinal cord stimulator trial results. Pain Med. 2000;1:110–115. [PubMed: 15101899] Sdrulla et al. Page 16 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
67. Alo KM, Chado HN. Effect of spinal cord stimulation on sensory nerve conduction threshold functional measures. Neuromodulation. 2000;3:145–154. [PubMed: 22151462]
68. de Andrade DC, Bendib B, Hattou M, Keravel Y, Nguyen JP, Lefaucheur JP. Neurophysiological assessment of spinal cord stimulation in failed back surgery syndrome. Pain. 2010;150:485–491. [PubMed: 20591571]
69. Nagel SJ, Wilson S, Johnson MD, Machado A, Frizon L, Chardon MK, et al. Spinal cord stimulation for spasticity: historical approaches, current status, and future directions. Neuromodulation. 2017;20:307–321. [PubMed: 28370802]
70. de Andrade EM, Ghilardi MG, Cury RG, Barbosa ER, Fuentes R, Teixeira MJ, et al. Spinal cord stimulation for Parkinson’s disease: a systematic review. Neurosurg Rev. 2016;39:27–35; discussion 35. [PubMed: 26219854]
71. Willer JC. Comparative study of perceived pain and nociceptive flexion reflex in man. Pain. 1977;3:69–80. [PubMed: 876668]
72. Sandrini G, Serrao M, Rossi P, Romaniello A, Cruccu G, Willer JC. The lower limb flexion reflex in humans. Prog Neurobiol. 2005;77:353–395. [PubMed: 16386347]
73. Garcia-Larrea L, Sindou M, Mauguiere F. Nociceptive flexion reflexes during analgesic neurostimulation in man. Pain. 1989;39:145–156. [PubMed: 2594393]
74. Garcia-Larrea L, Peyron R, Mertens P, Laurent B, Mauguiere F, Sindou M. Functional imaging and neurophysiological assessment of spinal and brain therapeutic modulation in humans. Arch Med Res. 2000;31:248–257. [PubMed: 11036174]
75. Bentley LD, Duarte RV, Furlong PL, Ashford RL, Raphael JH. Brain activity modifications following spinal cord stimulation for chronic neuropathic pain: A systematic review. Eur J Pain. 2016;20:499–511. [PubMed: 26424514]
76. Polacek H, Kozak J, Vrba I, Vrana J, Stancak A. Effects of spinal cord stimulation on the cortical somatosensory evoked potentials in failed back surgery syndrome patients. Clin Neurophysiol. 2007; 118:1291–1302. [PubMed: 17452003]
77. Buonocore M, Bodini A, Demartini L, Bonezzi C. Inhibition of somatosensory evoked potentials during spinal cord stimulation and its possible role in the comprehension of antalgic mechanisms of neurostimulation for neuropathic pain. Minerva Anestesiol. 2012;78:297–302. [PubMed: 22095108]
78. Wolter T, Kieselbach K, Sircar R, Gierthmuehlen M. Spinal cord stimulation inhibits cortical somatosensory evoked potentials significantly stronger than transcutaneous electrical nerve stimulation. Pain Physician. 2013;16:405–414. [PubMed: 23877457]
79. Blair RD, Lee RG, Vanderlinden G. Dorsal column stimulation. Its effect on the somatosensory evoked response. Arch Neurol. 1975;32:826–829. [PubMed: 1081871]
80. Theuvenet PJ, Dunajski Z, Peters MJ, van Ree JM. Responses to median and tibial nerve stimulation in patients with chronic neuropathic pain. Brain Topogr. 1999;11:305–313. [PubMed: 10449261]
81. Sufianov AA, Shapkin AG, Sufianova GZ, Elishev VG, Barashin DA, Berdichevskii VB, et al. Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord. Bull Exp Biol Med. 2014;157:462–465. [PubMed: 25113605]
82. Pluijms WA, Slangen R, van Kleef M, Joosten EA, Reulen JP. Increased contact heat evoked potential stimulation latencies in responders to spinal cord stimulation for painful diabetic polyneuropathy. Neuromodulation. 2015;18:126–132; discussion 132. [PubMed: 24945509]
83. Apkarian AV. Human brain imaging studies of chronic pain: translational opportunities In: Kruger L, Light AR, eds. Translational Pain Research: From Mouse to Man. Boca Raton, FL: CRC Press/ Taylor & Francis, LLC.; 2010.
84. Vachon-Presseau E, Centeno MV, Ren W, Berger SE, Tetreault P, Ghantous M, et al. The emotional brain as a predictor and amplifier of chronic pain. J Dent Res. 2016;95:605–612. [PubMed: 26965423]
85. Kiriakopoulos ET, Tasker RR, Nicosia S, Wood ML, Mikulis DJ. Functional magnetic resonance imaging: a potential tool for the evaluation of spinal cord stimulation: technical case report. Neurosurgery. 1997;41:501–504. [PubMed: 9257323] Sdrulla et al. Page 17 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
86. Moens M, Sunaert S, Marien P, Brouns R, De Smedt A, Droogmans S, et al. Spinal cord stimulation modulates cerebral function: an fMRI study. Neuroradiology. 2012;54:1399–1407. [PubMed: 22941431]
87. Stancak A, Kozak J, Vrba I, Tintera J, Vrana J, Polacek H, et al. Functional magnetic resonance imaging of cerebral activation during spinal cord stimulation in failed back surgery syndrome patients. Eur J Pain. 2008;12:137–148. [PubMed: 17977762]
88. Deogaonkar M, Sharma M, Oluigbo C, Nielson DM, Yang X, Vera-Portocarrero L, et al. Spinal cord stimulation (SCS) and functional magnetic resonance imaging (fMRI): modulation of cortical connectivity with therapeutic SCS. Neuromodulation. 2016;19:142–153. [PubMed: 26373920]
89. Meglio M, Cioni B, Visocchi M, Nobili F, Rodriguez G, Rosadini G, et al. Spinal cord stimulation and cerebral haemodynamics. Acta Neurochir (Wien). 1991;111:43–48. [PubMed: 1927623]
90. Mazzone P, Pisani R, Nobili F, Arrigo A, Gambaro M, Rodriguez G. Assessment of regional cerebral blood flow during spinal cord stimulation in humans. Stereotact Funct Neurosurg. 1995;64:197–201. [PubMed: 8817806]
91. Hosobuchi Y Electrical stimulation of the cervical spinal cord increases cerebral blood flow in humans. Appl Neurophysiol. 1985;48:372–376. [PubMed: 3879799]
92. Nagamachi S, Fujita S, Nishii R, Futami S, Wakamatsu H, Yano T, et al. Alteration of regional cerebral blood flow in patients with chronic pain--evaluation before and after epidural spinal cord stimulation. Ann Nucl Med. 2006;20:303–310. [PubMed: 16856574]
93. Kishima H, Saitoh Y, Oshino S, Hosomi K, Ali M, Maruo T, et al. Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H(2)15O PET study. Neuroimage. 2010;49:2564–2569. [PubMed: 19874903]
94. Guan Y Spinal cord stimulation: neurophysiological and neurochemical mechanisms of action. Current Pain Headache Rep. 2012;16:217–225.
95. Linderoth B, Meyerson BA. Spinal cord stimulation: exploration of the physiological basis of a widely used therapy. Anesthesiology. 2010;113:1265–1267. [PubMed: 21042195]
96. Meyerson BA, Cui JG, Yakhnitsa V, Sollevi A, Segerdahl M, Stiller CO, et al. Modulation of spinal pain mechanisms by spinal cord stimulation and the potential role of adjuvant pharmacotherapy. Sterotact Funct Neurosurg. 1997;68:129–140.
97. Meyerson BA, Linderoth B. Mode of action of spinal cord stimulation in neuropathic pain. J Pain Symptom Manage. 2006;31:S6–12. [PubMed: 16647596]
98. Zhang TC, Janik JJ, Grill WM. Mechanisms and models of spinal cord stimulation for the treatment of neuropathic pain. Brain Res. 2014;1569:19–31. [PubMed: 24802658]
99. Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1–32. [PubMed: 19400724]
100. Braz J, Solorzano C, Wang X, Basbaum AI. Transmitting pain and itch messages: a contemporary view of the spinal cord circuits that generate gate control. Neuron. 2014;82:522–536. [PubMed: 24811377]
101. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288:1765– 1769. [PubMed: 10846153]
102. Duggan AW, Foong FW. Bicuculline and spinal inhibition produced by dorsal column stimulation in the cat. Pain. 1985;22:249–259. [PubMed: 2993983]
103. Cui JG, Linderoth B, Meyerson BA. Effects of spinal cord stimulation on touch-evoked allodynia involve GABAergic mechanisms. An experimental study in the mononeuropathic rat. Pain. 1996;66:287–295. [PubMed: 8880852]
104. Cui JG, O’Connor WT, Ungerstedt U, Linderoth B, Meyerson BA. Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in mononeuropathy via a GABAergic mechanism. Pain. 1997;73:87–95. [PubMed: 9414060]
105. Stiller CO, Cui JG, O’Connor WT, Brodin E, Meyerson BA, Linderoth B. Release of gammaaminobutyric acid in the dorsal horn and suppression of tactile allodynia by spinal cord stimulation in mononeuropathic rats. Neurosurgery. 1996;39:367–374; discussion 374–365. [PubMed: 8832675] Sdrulla et al. Page 18 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
106. Schechtmann G, Lind G, Winter J, Meyerson BA, Linderoth B. Intrathecal clonidine and baclofen enhance the pain-relieving effect of spinal cord stimulation: a comparative placebocontrolled, randomized trial. Neurosurgery. 2010;67:173–181. [PubMed: 20559103] 107. Lind G, Meyerson BA, Winter J, Linderoth B. Intrathecal baclofen as adjuvant therapy to enhance the effect of spinal cord stimulation in neuropathic pain: a pilot study. European J Pain. 2004;8:377–383. [PubMed: 15207519]
108. Schechtmann G, Song Z, Ultenius C, Meyerson BA, Linderoth B. Cholinergic mechanisms involved in the pain relieving effect of spinal cord stimulation in a model of neuropathy. Pain. 2008;139:136–145. [PubMed: 18472215]
109. Schechtmann G, Wallin J, Meyerson BA, Linderoth B. Intrathecal clonidine potentiates suppression of tactile hypersensitivity by spinal cord stimulation in a model of neuropathy. Anesth Analg. 2004;99:135–139. [PubMed: 15281519]
110. Linderoth B, Gazelius B, Franck J, Brodin E. Dorsal column stimulation induces release of serotonin and substance P in the cat dorsal horn. Neurosurgery. 1992;31:289–296; discussion 296–287. [PubMed: 1381066]
111. Song Z, Ultenius C, Meyerson BA, Linderoth B. Pain relief by spinal cord stimulation involves serotonergic mechanisms: an experimental study in a rat model of mononeuropathy. Pain. 2009;147:241–248. [PubMed: 19836134]
112. Song Z, Meyerson BA, Linderoth B. Spinal 5-HT receptors that contribute to the pain- relieving effects of spinal cord stimulation in a rat model of neuropathy. Pain. 2011;152:1666–1673. [PubMed: 21514998]
113. Sato KL, King EW, Johanek LM, Sluka KA. Spinal cord stimulation reduces hypersensitivity through activation of opioid receptors in a frequency-dependent manner. Eur J Pain. 2013;17:551–561. [PubMed: 23065849]
114. Inoue S, Johanek LM, Sluka KA. Lack of analgesic synergy of the cholecystokinin receptor antagonist proglumide and spinal cord stimulation for the treatment of neuropathic pain in rats. Neuromodulation. 2017;20:534–542. [PubMed: 28393429]
115. Sun L, Tai L, Qiu Q, Mitchell R, Fleetwood-Walker S, Joosten EA, et al. Endocannabinoid activation of CB1 receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation. Eur J Pain. 2017.
116. Guan Y, Wacnik PW, Yang F, Carteret AF, Chung CY, Meyer RA, et al. Spinal cord stimulationinduced analgesia: electrical stimulation of dorsal column and dorsal roots attenuates dorsal horn neuronal excitability in neuropathic rats. Anesthesiology. 2010; 113:1392–1405. [PubMed: 21068658]
117. Yakhnitsa V, Linderoth B, Meyerson BA. Spinal cord stimulation attenuates dorsal horn neuronal hyperexcitability in a rat model of mononeuropathy. Pain. 1999;79:223–233. [PubMed: 10068168]
118. Dougherty PM, Willis WD. Enhanced responses of spinothalamic tract neurons to excitatory amino acids accompany capsaicin-induced sensitization in the monkey. J Neurosci. 1992;12:883– 894. [PubMed: 1545244]
119. Simone DA, Sorkin LS, Oh U, Chung JM, Owens C, LaMotte RH, et al. Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons. J Neurophysiol. 1991;66:228–246. [PubMed: 1919669]
120. Sdrulla AD, Xu Q, He SQ, Tiwari V, Yang F, Zhang C, et al. Electrical stimulation of lowthreshold afferent fibers induces a prolonged synaptic depression in lamina II dorsal horn neurons to high-threshold afferent inputs in mice. Pain. 2015;156:1008–1017. [PubMed: 25974163]
121. Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol. 2001;63:569–611. [PubMed: 11164622]
122. Yang F, Xu Q, Shu B, Tiwari V, He SQ, Vera-Portocarrero LP, et al. Activation of cannabinoid CB1 receptor contributes to suppression of spinal nociceptive transmission and inhibition of mechanical hypersensitivity by Abeta-fiber stimulation. Pain. 2016;157:2582–2593. [PubMed: 27589093] Sdrulla et al. Page 19 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
123. Zhang TC, Janik JJ, Peters RV, Chen G, Ji RR, Grill WM. Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control. J Neurophysiol. 2015:jn.00147.02015.
124. Yakhnista VA, Linderoth B, Meyerson BA. Modulation of dorsal horn neuronal activity by spinal cord stimulation in a rat model of neuropathy: The role of the dorsal funicles. Neurophysiology. 1998;30:424–427.
125. Saade NE, Tabet MS, Soueidan SA, Bitar M, Atweh SF, Jabbur SJ. Supraspinal modulation of nociception in awake rats by stimulation of the dorsal column nuclei. Brain Res. 1986;369:307– 310. [PubMed: 3697746]
126. Barchini J, Tchachaghian S, Shamaa F, Jabbur SJ, Meyerson BA, Song Z, et al. Spinal segmental and supraspinal mechanisms underlying the pain-relieving effects of spinal cord stimulation: an experimental study in a rat model of neuropathy. Neuroscience. 2012;215:196–208. [PubMed: 22548781]
127. Song Z, Ansah OB, Meyerson BA, Pertovaara A, Linderoth B. The rostroventromedial medulla is engaged in the effects of spinal cord stimulation in a rodent model of neuropathic pain. Neuroscience. 2013;247:134–144. [PubMed: 23711584]
128. Song Z, Ansah OB, Meyerson BA, Pertovaara A, Linderoth B. Exploration of supraspinal mechanisms in effects of spinal cord stimulation: role of the locus coeruleus. Neuroscience. 2013;253:426–434. [PubMed: 24036376]
129. Tiede J, Brown L, Gekht G, Vallejo R, Yearwood T, Morgan D. Novel spinal cord stimulation parameters in patients with predominant back pain. Neuromodulation. 2013;16:370–375. [PubMed: 23433237]
130. Van Buyten JP, Al-Kaisy A, Smet I, Palmisani S, Smith T. High-frequency spinal cord stimulation for the treatment of chronic back pain patients: results of a prospective multicenter European clinical study. Neuromodulation. 2013;16:59–65; discussion 65–56. [PubMed: 23199157]
131. Al-Kaisy A, Van Buyten JP, Smet I, Palmisani S, Pang D, Smith T. Sustained effectiveness of 10 kHz high-frequency spinal cord stimulation for patients with chronic, low back pain: 24-month results of a prospective multicenter study. Pain Med. 2014;15:347–354. [PubMed: 24308759]
132. Kinfe TM, Pintea B, Link C, Roeske S, Guresir E, Guresir A, et al. High frequency (10 kHz) or burst spinal cord stimulation in failed back surgery syndrome patients with predominant back pain: preliminary data from a prospective observational study. Neuromodulation. 2016;19:268– 275. [PubMed: 26762585]
133. Al-Kaisy A, Palmisani S, Smith TE, Carganillo R, Houghton R, Pang D, 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. Pain Med. 2017. 134. Russo M, Verrills P, Mitchell B, Salmon J, Barnard A, Santarelli D. High frequency spinal cord stimulation at 10 kHz for the treatment of chronic pain: 6-month Australian clinical experience. Pain Physician. 2016;19:267–280. [PubMed: 27228514]
135. Rapcan R, Mlaka J, Venglarcik M, Vinklerova V, Gajdos M, Illes R. High-frequency - spinal cord stimulation. Bratisl Lek Listy. 2015;116:354–356. [PubMed: 26084736]
136. De Andres J, Monsalve-Dolz V, Fabregat-Cid G, Villanueva-Perez V, Harutyunyan A, AsensioSamper JM, et al. Prospective, randomized blind effect-on-outcome study of conventional vs high-frequency spinal cord stimulation in patients with pain and disability due to failed back surgery syndrome. Pain Med. 2017;18:2401–2421. [PubMed: 29126228]
137. Lambru G, Trimboli M, Palmisani S, Smith T, Al-Kaisy A. Safety and efficacy of cervical 10 kHz spinal cord stimulation in chronic refractory primary headaches: a retrospective case series. J Headache Pain. 2016;17:66. [PubMed: 27393015]
138. Arcioni R, Palmisani S, Mercieri M, Vano V, Tigano S, Smith T, et al. Cervical 10 kHz spinal cord stimulation in the management of chronic, medically refractory migraine: A prospective, open-label, exploratory study. Eur J Pain. 2016;20:70–78. [PubMed: 25828556]
139. Al-Kaisy A, Palmisani S, Smith T, Harris S, Pang D. The use of 10-kilohertz spinal cord Stimulation in a cohort of patients with chronic neuropathic limb pain refractory to medical management. Neuromodulation. 2015;18:18–23; discussion 23. [PubMed: 25257382] Sdrulla et al. Page 20 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
140. Chakravarthy K, Nava A, Christo PJ, Williams K. Review of recent advances in peripheral nerve stimulation (PNS). Curr Pain Headache Rep. 2016;20:60. [PubMed: 27671799]
141. Xu J, Liu A, Cheng J. New advancements in spinal cord stimulation for chronic pain management. Curr Opin Anaesthesiol. 2017;30:710–717. [PubMed: 28938297]
142. Kapural L, Peterson E, Provenzano DA, Staats P. Clinical evidence for spinal cord stimulation for failed back surgery syndrome (FBSS): systematic review. Spine (Phila Pa 1976). 2017;42 Suppl 14:S61–s66. [PubMed: 28441313]
143. Youn Y, Smith H, Morris B, Argoff C, Pilitsis JG. The effect of high-frequency stimulation on sensory thresholds in chronic pain patients. Stereotact Funct Neurosurg. 2015;93:355–359. [PubMed: 26444968]
144. Buonocore M, Demartini L. Inhibition of somatosensory evoked potentials during different modalities of spinal cord stimulation: a case report. Neuromodulation. 2016;19:882–884. [PubMed: 26762589]
145. Chakravarthy K, Richter H, Christo PJ, Williams K, Guan Y. Spinal cord stimulation for treating chronic pain: reviewing preclinical and clinical data on paresthesia-free high-frequency therapy. Neuromodulation. 2017.
146. Kilgore KL, Bhadra N. Nerve conduction block utilising high-frequency alternating current. Med Biol Eng Comput. 2004;42:394–406. [PubMed: 15191086]
147. Lempka SF, McIntyre CC, Kilgore KL, Machado AG. Computational analysis of kilohertz frequency spinal cord stimulation for chronic pain management. Anesthesiology. 2015;122:1362– 1376. [PubMed: 25822589]
148. Song Z, Viisanen H, Meyerson BA, Pertovaara A, Linderoth B. Efficacy of kilohertz- frequency and conventional spinal cord stimulation in rat models of different pain conditions. Neuromodulation. 2014;17:226–234; discussion 234–225. [PubMed: 24612269]
149. Crosby ND, Janik JJ, Grill WM. Modulation of activity and conduction in single dorsal column axons by kilohertz-frequency spinal cord stimulation. J Neurophysiol. 2017;117:136–147. [PubMed: 27760823]
150. Maeda Y, Ikeuchi M, Wacnik P, Sluka KA. Increased c-fos immunoreactivity in the spinal cord and brain following spinal cord stimulation is frequency-dependent. Brain Res. 2009;1259:40– 50. [PubMed: 19161992]
151. Shechter R, Yang F, Xu Q, Cheong YK, He SQ, Sdrulla A, et al. Conventional and kilohertzfrequency spinal cord stimulation produces intensity- and frequency-dependent inhibition of mechanical hypersensitivity in a rat model of neuropathic pain. Anesthesiology. 2013;119:422– 432. [PubMed: 23880991]
152. Li S, Farber JP, Linderoth B, Chen J, Foreman RD. Spinal cord stimulation with “conventional clinical” and higher frequencies on activity and responses of spinal neurons to noxious stimuli: an animal study. Neuromodulation. 2017.
153. De Carolis G, Paroli M, Tollapi L, Doust MW, Burgher AH, Yu C, et al. Paresthesiaindependence: an assessment of technical factors related to 10 kHz paresthesia-free spinal cord stimulation. Pain Physician. 2017;20:331–341. [PubMed: 28535555]
154. Hou S, Kemp K, Grabois M. A systematic evaluation of burst spinal cord stimulation for chronic back and limb pain. Neuromodulation. 2016.
155. De Ridder D, Vanneste S. Response: A systematic evaluation of burst spinal cord stimulation for chronic back and limb pain. Neuromodulation. 2016;19:785–786. [PubMed: 27704690]
156. De Ridder D, Vanneste S, Plazier M, Vancamp T. Mimicking the brain: evaluation of St Jude Medical’s Prodigy Chronic Pain System with Burst Technology. Expert Rev Med Devices. 2015;12:143–150. [PubMed: 25483825]
157. Schu S, Slotty PJ, Bara G, von Knop M, Edgar D, Vesper J. A prospective, randomised, doubleblind, placebo-controlled study to examine the effectiveness of burst spinal cord stimulation patterns for the treatment of failed back surgery syndrome. Neuromodulation. 2014;17:443–450. [PubMed: 24945621]
158. Kriek N, Groeneweg JG, Stronks DL, de Ridder D, Huygen FJ. Preferred frequencies and waveforms for spinal cord stimulation in patients with complex regional pain syndrome: A Sdrulla et al. Page 21 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript multicentre, double-blind, randomized and placebo-controlled crossover trial. Eur J Pain. 2017;21:507–519. [PubMed: 27714945]
159. Muhammad S, Roeske S, Chaudhry SR, Kinfe TM. Burst or high-frequency (10 kHz) spinal cord stimulation in failed back surgery syndrome patients with predominant back pain: one year comparative data. Neuromodulation. 2017;20:661–667. [PubMed: 28544182]
160. De Ridder D, Vanneste S. Burst and tonic spinal cord stimulation: different and common brain mechanisms. Neuromodulation. 2016;19:47–59. [PubMed: 26586145]
161. Tang R, Martinez M, Goodman-Keiser M, Farber JP, Qin C, Foreman RD. Comparison of burst and tonic spinal cord stimulation on spinal neural processing in an animal model. Neuromodulation. 2014;17:143–151. [PubMed: 24655042]
162. Crosby ND, Goodman Keiser MD, Smith JR, Zeeman ME, Winkelstein BA. Stimulation parameters define the effectiveness of burst spinal cord stimulation in a rat model of neuropathic pain. Neuromodulation. 2015;18:1–8; discussion 8. [PubMed: 25145400]
163. Crosby ND, Weisshaar CL, Smith JR, Zeeman ME, Goodman-Keiser MD, Winkelstein BA. Burst and tonic spinal cord stimulation differentially activate GABAergic mechanisms to attenuate pain in a rat model of cervical radiculopathy. IEEE Trans Biomed Eng. 2015;62:1604–1613. [PubMed: 25667344]
164. Meuwissen KPV, Gu JW, Zhang TC, Joosten EAJ. Conventional-SCS vs. burst-SCS and the behavioral effect on mechanical hypersensitivity in a rat model of chronic neuropathic pain: effect of amplitude. Neuromodulation. 2017.
165. Deer TR, Grigsby E, Weiner RL, Wilcosky B, Kramer JM. A prospective study of dorsal root ganglion stimulation for the relief of chronic pain. Neuromodulation. 2013;16:67–71; discussion 71–62. [PubMed: 23240657]
166. Liem L, Russo M, Huygen FJPM, Van Buyten J-P, Smet I, Verrills P, 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. Neuromodulation. 2013;16:471–482. [PubMed: 23668228]
167. Liem L, Russo M, Huygen FJ, Van Buyten JP, Smet I, Verrills P, et al. One-year outcomes of spinal cord stimulation of the dorsal root ganglion in the treatment of chronic neuropathic pain. Neuromodulation. 2015;18:41–48; discussion 48–49. [PubMed: 25145467]
168. Liem L, Mekhail N. Management of Postherniorrhaphy Chronic Neuropathic Groin Pain: A Role for Dorsal Root Ganglion Stimulation. Pain Pract. 2016;16:915–923. [PubMed: 26914499]
169. Schu S, Gulve A, ElDabe S, Baranidharan G, Wolf K, Demmel W, et al. Spinal cord stimulation of the dorsal root ganglion for groin pain-a retrospective review. Pain Pract. 2015;15:293–299. [PubMed: 24690212]
170. Van Buyten JP, Smet I, Liem L, Russo M, Huygen F. Stimulation of dorsal root ganglia for the management of complex regional pain syndrome: a prospective case series. Pain Pract. 2015;15:208–216. [PubMed: 24451048]
171. Koopmeiners AS, Mueller S, Kramer J, Hogan QH. Effect of electrical field stimulation on dorsal root ganglion neuronal function. Neuromodulation. 2013;16:304–311; discussion 310–301. [PubMed: 23421796]
172. Pan B, Yu H, Fischer GJ, Kramer JM, Hogan QH. Dorsal root ganglionic field stimulation relieves spontaneous and induced neuropathic pain in rats. J Pain. 2016;17:1349–1358. [PubMed: 27687223]
173. Pawela CP, Kramer JM, Hogan QH. Dorsal root ganglion stimulation attenuates the BOLD signal response to noxious sensory input in specific brain regions: insights into a possible mechanism for analgesia. Neuroimage. 2017;147:10–18. [PubMed: 27876655]
174. Sweet J, Badjatiya A, Tan D, Miller J. Paresthesia-free high-density spinal cord stimulation for postlaminectomy syndrome in a prescreened population: a prospective case series. Neuromodulation. 2016;19:260–267. [PubMed: 26481726]
175. Provenzano DA, Rebman J, Kuhel C, Trenz H, Kilgore J. The efficacy of high-density spinal cord stimulation among trial, implant, and conversion patients: a retrospective case series. Neuromodulation. 2017;20:654–660. [PubMed: 28547853] Sdrulla et al. Page 22 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
176. Wille F, Breel JS, Bakker EW, Hollmann MW. Altering conventional to high density spinal cord stimulation: an energy dose-response relationship in neuropathic pain therapy. Neuromodulation. 2017;20:71–80. [PubMed: 27778413]
177. Aiudi CM, Dunn RY, Burns SM, Roth SA, Opalacz A, Zhang Y, et al. Loss of efficacy to spinal cord stimulator therapy: clinical evidence and possible causes. Pain Physician. 2017;20:E1073– e1080. [PubMed: 29149152]
178. Mann SA, Sparkes E, Duarte RV, Raphael JH. Attrition with spinal cord stimulation. Br J Neurosurg. 2015;29:823–828. [PubMed: 26087397]
179. Celestin J, Edwards RR, Jamison RN. Pretreatment psychosocial variables as predictors of outcomes following lumbar surgery and spinal cord stimulation: a systematic review and literature synthesis. Pain Med. 2009;10:639–653. [PubMed: 19638142]
180. Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123:231–243. [PubMed: 16697110]
181. von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012;73:638–652. [PubMed: 22365541]
182. Demant DT, Lund K, Vollert J, Maier C, Segerdahl M, Finnerup NB, et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, doubleblind, placebo-controlled phenotype-stratified study. Pain. 2014;155:2263–2273. [PubMed: 25139589]
183. North JM, Hong KJ, Cho PY. Clinical outcomes of 1 kHz subperception spinal cord stimulation in implanted patients with failed paresthesia-based stimulation: results of a prospective randomized controlled trial. Neuromodulation. 2016;19:731–737. [PubMed: 27186822]
184. Lind G, Linderoth B. Pharmacologically enhanced spinal cord stimulation for pain: an evolving strategy. Pain Manag. 2011;1:441–449. [PubMed: 24645711]
185. De Ridder D, Perera S, Vanneste S. Are 10 kHz stimulation and burst stimulation fundamentally the same? Neuromodulation. 2017;20:650–653. [PubMed: 28544432]
186. Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. 2008;136:380–387. [PubMed: 17888574]
187. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:162–173. [PubMed: 25575710]
188. Jensen MP, Chodroff MJ, Dworkin RH. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology. 2007;68:1178–1182. [PubMed: 17420400] 189. Bonnie RJ, Kesselheim AS, Clark DJ. Both urgency and balance needed in addressing opioid epidemic: a report from the National Academies of Sciences, Engineering, and Medicine. JAMA. 2017;318:423–424. [PubMed: 28715551]
190. Manchikanti L, Helm S, 2nd, Fellows B, Janata JW, Pampati V, Grider JS, et al. Opioid epidemic in the United States. Pain Physician. 2012;15:ES9–ES38. [PubMed: 22786464]
191. Turner JA, Deyo RA, Loeser JD. Spinal cord stimulation: stimulating questions. Pain. 2007;132:10–11. [PubMed: 17845834]
192. Biurrun Manresa JA, Sorensen J, Andersen OK, Arendt-Nielsen L, Gerdle B. Dynamic changes in nociception and pain perception after spinal cord stimulation in chronic neuropathic pain patients. Clin J Pain. 2015;31:1046–1053. [PubMed: 25789414]
193. Song Z, Meyerson BA, Linderoth B. Muscarinic receptor activation potentiates the effect of spinal cord stimulation on pain-related behavior in rats with mononeuropathy. Neurosci Lett. 2008;436:7–12. [PubMed: 18343581]
194. Song Z, Meyerson BA, Linderoth B. The interaction between antidepressant drugs and the painrelieving effect of spinal cord stimulation in a rat model of neuropathy. Anesth Analg. 2011;113:1260–1265. [PubMed: 21788322]
195. Baba H, Yoshimura M, Nishi S, Shimoji K. Synaptic responses of substantia gelatinosa neurones to dorsal column stimulation in rat spinal cord in vitro. J Physiol. 1994;478 ( Pt 1):87–99. [PubMed: 7965839] Sdrulla et al. Page 23 Pain Pract. Author manuscript; available in PMC 2019 February 27. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
196. Shimoji K, Shimizu H, Maruyama Y, Matsuki M, Kuribayashi H, Fujioka H. Dorsal column stimulation in man: facilitation of primary afferent depolarization. Anesth Analg. 1982;61:410– 413. [PubMed: 7199863]
197. Yang F, Xu Q, Cheong YK, Shechter R, Sdrulla A, He SQ, et al. Comparison of intensitydependent inhibition of spinal wide-dynamic range neurons by dorsal column and peripheral nerve stimulation in a rat model of neuropathic pain. Eur J Pain. 2014.
198. Wallin J, Fiska A, Tjolsen A, Linderoth B, Hole K. Spinal cord stimulation inhibits long-term potentiation of spinal wide dynamic range neurons. Brain Res. 2003;973:39–43. [PubMed: 12729951]
199. Sato KL, Johanek LM, Sanada LS, Sluka KA. Spinal cord stimulation reduces mechanical hyperalgesia and glial cell activation in animals with neuropathic pain. Anesth Analg. 2014;118:464–472. [PubMed: 24361846]
200. Rees H, Roberts MH. Activation of cells in the anterior pretectal nucleus by dorsal column stimulation in the rat. J Physiol. 1989;417:361–373. [PubMed: 2621599]
201. Saade NE, Barchini J, Tchachaghian S, Chamaa F, Jabbur SJ, Song Z, et al. The role of the dorsolateral funiculi in the pain relieving effect of spinal cord stimulation: a study in a rat model of neuropathic pain. Exp Brain Res. 2015;233:1041–1052. [PubMed: 25537469]
202. Arle JE, Mei L, Carlson KW, Shils JL. High-frequency stimulation of dorsal column axons: potential underlying mechanism of paresthesia-free neuropathic pain relief. Neuromodulation. 2016.
