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山东省立医院疼痛科英语晨读已经坚持10余年的时间了，每天交班前15分钟都会精选一篇英文文献进行阅读和翻译。一是可以保持工作后的英语阅读习惯，二是可以学习前沿的疼痛相关知识。我们会将晨读内容与大家分享，助力疼痛学习。
本次文献选自Raghu ALB, Parker T, Aziz TZ, et al. Invasive Electrical Neuromodulation for the Treatment of Painful Diabetic Neuropathy: Systematic Review and Meta-Analysis. Neuromodulation, 2021; 24: 13–21。本次学习由谢珺田副主任医师主讲。
Tonic-SCS trials cannot be blinded as stimulation leads to paraesthesia over the targeted area. This may well generate important placebo and nocebo bias. HF-SCS and b-SCS do not typically result in paraesthesia, so that the presence of stimulation is imperceptible to the patient in every respect other than the pain relief that it may provide. From a researcher’s perspective this offers a major advantage, as double-blind trials can be designed where all participants have a system implanted but stimulation is initially randomized to on or off. Those participants in the off group are effectively sham operated controls, but without the ethical concerns that sham surgery normally raises as they have working systems which can all eventually be activated. Crossover designs are also possible. The relative efficacy of these different SCS paradigms is unknown, but preliminary research suggests that they could be noninferior to t-SCS, and preferable for some patients. An RCT of HF-SCS for PDN is currently underway (clinicaltrials.gov: NCT03228420).
张力性SCS研究难以采取盲法，因为刺激会导致靶区感觉异常。这很可能带来安慰剂偏倚和观察者期望效应偏倚。HF-SCS和b-SCS通常不产生感觉异常，因此，除了可提供疼痛缓解以外，患者在各个方面都无法察觉到刺激的存在。从临床研究的角度来看，这显然是一个重要的优势，因为可以设计双盲试验，所有参与者都植入SCS系统，但预先设定刺激随机分为开或关。刺激关闭的参与者实际上是假手术对照组，但没有假手术通常引起的伦理问题，因为他们最终都能激活工作系统。交叉设计也是可能的。这些不同SCS模式的相对有效性尚不清楚，但初步研究表明，它们可能不劣于t-SCS，对某些患者更有优势。目前正在进行HF-SCS用于PDN的RCT（clinicaltrials.gov:NCT03228420）。
The DRG is a well-recognized locus of dysfunction in neuropathic pain syndromes. The ACCURATE trial demonstrated that DRGS was superior to t-SCS for treatment of complex regional pain syndrome (CRPS), another cause of neuropathic pain in the foot. This was achieved whilst largely avoiding common side effects of t-SCS, including paraesthesias outside the target area and postural variation in stimulus intensity. Although CRPS and PDN are both neuropathic pain syndromes, their peripheral pathology is very different, and at present it is unclear whether or not the results of the ACCURATE trial will be replicated for PDN. Our analysis of a small number of patients suggests that DRGS is likely to have similar efficacy to t-SCS, although the large CI’s make this comparison largely speculative. The ongoing UK multicenter PENTAGONS trial (isrctn.com: ISRCTN40062191) aims to evaluate DRGS for PDN compared to BMT. DRGS is a slightly more technically challenging procedure than SCS, for which there is a learning curve for individual surgeons. In the ACCURATE RCT, there was a higher rate of procedure-related nonserious adverse events in the DRGS group than the SCS group; however, there was no difference in serious adverse event rates. Complications of dural puncture have been reported, however in experienced centers, these are rare occurrences when implanting DRGS electrodes, and safety is reportedly on par with SCS. Although more economical stimulation paradigms for SCS are being developed, DRGS benefits from markedly (~90%) lower energy consumption than typical SCS, largely due to the negligible layer of subdural cerebrospinal fluid at the DRG. This can be further optimized with prudent DRG electrode placement. This decreases the clinical and economic burden of IPG replacements: the most expensive hardware component.
DRG是神经性疼痛综合征中公认的功能障碍位点。确认研究结果表明，DRGS在治疗复杂区域性疼痛综合征（CRPS）方面优于t-SCS，CRPS是引起足部神经病理性疼痛的另一个原因。DRGS在很大程度上避免了t-SCS的常见副作用，包括靶区外的感觉异常和刺激强度随姿势而变化。虽然CRPS和PDN都是神经病理性疼痛综合征，但它们的周围神经病理学有很大的不同，目前尚不清楚准确的试验结果是否能用于PDN。我们对少数患者的分析表明，DRGS可能具有与t-SCS相似的疗效，尽管较大的可信区间使得这种比较在很大程度上是推测性的。正在进行的英国多中心协作研究（isrctn.com:ISRCTN40062191）旨在评估比较DRGS与BMT治疗PDN的效果。DRGS在技术上比SCS更具挑战性，对于个体外科医生来说有一个学习曲线。在准确的随机对照试验中，DRGS组的非严重不良事件发生率高于SCS组；然而，严重不良事件发生率没有差异。硬脑膜损伤的并发症已有报道，但是在经验丰富的临床中心，当植入DRGS电极时，这些并发症是罕见的，并且据报道安全性与SCS相当。尽管目前正在开发更适用的SCS的刺激模式，但DRGS的能量消耗比传统的SCS显著降低（~90%），这主要是由于DRG的硬膜下脑脊液层可以忽略不计。这可以通过谨慎的DRG电极放置来进一步优化。这减少了IPG替代品的临床和经济负担：最昂贵的硬件组件。
Diabetic neuropathy is frequently accompanied by peripheral vascular disease (PVD), and both pathologies, in variable combinations, may contribute to an individual’s limb pain. SCS is licensed to treat ischaemic pain due to medically refractory PVD and in that setting has long been recognized as vasoactive, improving microcirculatory blood flow. While the pathology of peripheral diabetic vasculopathy/neuropathy has been shown to involve both sympathetic and parasympathetic abnormalities, their relative mechanistic contributions to microcirculatory deficits remain uncertain. Arterio-venous shunts in the skin are under the control of the sympathetic nervous system. However by the time a patient develops PDN, their small-fiber loss will have left them largely peripherally sympathectomized, with highly impaired cutaneous microvascular dilatation and constriction, and compromised tissue perfusion. The demonstration of SCS-induced vasodilation at high intensities in sympathectomized animal models provides evidence that stimulation may improve cutaneous oxygenation by non-autonomically mediated means. DRGS may also improve tissue oxygenation. Retrograde firing in sensory fibers triggering vasodilator release, such as CRGP, may underpin such vasodilatation. Physiologically this is part of the axon reflex that causes increased perfusion in the skin surrounding an area of injury.
糖尿病周围神经病变常伴有血管疾病（PVD），这两种疾病可以并存，二者的病理变化可能共同导致患者的肢体疼痛。SCS被许可用于治疗药物难治性PVD引起的缺血性疼痛，在这种情况下，SCS长期被认为具有血管活性，改善微循环血流量。虽然周围型糖尿病血管病变/神经病变的病理学已被证明涉及交感神经和副交感神经异常，但它们导致微循环障碍的相应机制仍不明确。皮肤的动静脉分流受交感神经系统的控制。然而，当患者发展成PDN时，细小纤维丢失将使其大部分周围交感神经纤维受损，皮肤微血管扩张和收缩严重紊乱，组织灌注不良。在交感神经毁损的动物模型中，SCS诱导的高强度血管舒张的结果提供了电刺激可以通过非自主介导的方式改善皮肤氧合的证据。DRGS还可以直接改善组织氧合。感觉纤维的逆行放电触发血管扩张因子释放，如CRGP，可能是这种血管扩张的基础。生理学上这是轴突反射的一部分，轴突反射导致损伤区域周围皮肤灌注增加。
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