脊髓电刺激治疗慢性神经病理性疼痛的作用机制、作用靶点和作用模式（七）

 英语晨读 ·

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Joosten EA, Franken G. Spinal cord stimulation in chronic neuropathic pain: mechanisms of action, new locations, new paradigms. Pain. 2020 Sep;161 Suppl 1(1):S104-S113.本次学习由李芸主治医师主讲。

4.2. High-frequency spinal cord stimulation in neuropathic pain

High-frequency SCS is generally applied at a frequency above 1000 Hz, up until 10 kHz, with a pulse width at approximately 30 µs and an amplitude of typically 1 to 5 mA. Hypotheses about the underlying mechanism of HF SCS vary.

4.2.高频SCS

高频SCS通常以高于1000 Hz的频率施加，直到10 kHz，脉冲宽度约为30 ms，振幅通常为1至5 mA。关于高频SCS潜在机制的假设各不相同。

Although Tonic SCS and its pain inhibition is accompanied by paresthesias, the subthreshold HF SCS paradigm is paresthesia-free (administered below sensory threshold) and does not activate or change the conduction properties of the dorsal column Aβ fibers. Experimental research has shown that the dorsal column nuclei are activated with use of Tonic SCS, while with subthreshold HF SCS, the neurons in the gracile nucleus do not show a reduction of evoked responses upon peripheral stimulation in a chronic neuropathic pain model. A hypothetical mechanism for HF SCS and its pain-relieving effect was brought forward by Chakravarthy et al., who suggested that the electrical current applied to the spinal cord surface may generate a weak and localized electric field of electrochemical disturbance in the spinal dorsal horn and dorsal root entry zone. Hence, HF SCS in fact desynchronizes the communication between the nociceptive C fibers, which mainly terminate in the dorsal horn superficial laminae (Lamina 1-3), and the nociceptive specific neurons (Fig. 1). Besides the generation of a weak electrical field in the superficial dorsal horn, the hypotheses about the underlying mechanism of HF SCS also include (1) temporal summation which could play a role, where multiple pulses build on each other to achieve neuronal activation, and (2) a depolarization blockade that might occur and where propagating action potentials are differentially blocked by the HF stimulation.

虽然传统SCS及其疼痛抑制伴有感觉异常，但阈下HF-SCS模式无感觉异常（在感觉阈值以下施用），不会激活或改变背柱Aβ纤维的传导特性。实验研究表明，在慢性神经病理性疼痛模型中，使用传统SCS可激活背柱核，而使用阈下HF SCS时，股薄核中的神经元在外周刺激时未显示出诱发反应的减少。Chakravarthy等人提出了HF SCS及其止痛效果的假设机制，他认为施加到脊髓表面的电流可能会在脊髓背角和背根进入区产生微弱的局部电化学干扰电场。因此，HF SCS事实上使伤害性C纤维（主要终止于背角浅层（层1-3））和伤害性特异性神经元之间的通信失去同步。除了在浅背角产生弱电场外，关于HF-SCS潜在机制的假设还包括：（1）时间求和，这可能起到一定作用，其中多个脉冲相互叠加以实现神经元激活，和（2）可能发生的去极化阻断，其中传播动作电位被HF刺激差分阻断。

Until today, the optimal frequency for HF SCS has not yet been determined, and clinical evidence suggests that different HF SCS frequencies can yield clinically significant pain relief.

直到今天，HF SCS的最佳频率尚未确定，临床证据表明，不同的HF SCS频率可以产生临床显著的疼痛缓解。

4.3. Burst spinal cord stimulation in neuropathic pain

The Burst paradigm was introduced in 2010 by de Ridder et al. This Burst waveform consists of 5 closely spaced monophasic spikes administered at 40 Hz interburst mode and 500 Hz intraburst frequency, with a pulse width of 1 ms and 1 ms interspike interval, delivered in constant current mode. The cumulative charge of the five 1 ms spikes is balanced during the 5 ms after the spikes, in a so-called passive recharge phase, which differentiates it from HF SCS and Tonic SCS, in which each pulse is immediately charge balanced after each spike, in a so-called active recharge phase. This Burst pattern was chosen because it supposedly mimics naturally occurring neural bursting patterns in the central nervous system. Indeed, neurons responsible for encoding aspects of nociception from peripheral neurons and the thalamus have been reported to fire in bursting patterns. Although possible overlap between the original Burst waveform (as proposed and used by De Ridder et al.) and the neural bursting patterns in the central nervous system, it is important to note that Burst parameters have not yet been optimized in relation to pain-relieving capacity because the parameter space has not been fully explored. For instance, effect differences of active vs passive charge recovery have not been characterized. Beyond charge recovery, many other parameters can be varied: interburst frequency, intraburst frequency, pulse width, shape of pulse, but also the number of pulses. Future research is needed to optimize burst programming as well as to elucidate how the physiological changes produced by different Burst SCS paradigms are reflected in preclinical behavior and in the clinic.

4.3.爆冲式SCS

de Ridder等人于2010年引入了爆冲式SCS。该突发波形由5个紧密间隔的单相尖峰组成，以40 Hz脉冲串间模式和500 Hz脉冲串内频率给予，脉冲宽度为1 ms，脉冲间隔为1 ms。以恒定电流模式提供。5个1ms尖峰的累积电荷在尖峰后的5ms内充电，处于所谓的被动再充电阶段，这将其与HF SCS和Tonic SCS区分开来，在HF SCS和Tonic SC中，每个脉冲在每个尖峰后立即电荷平衡，处于一个所谓的主动再充电阶段。之所以选择这种爆冲式SCS，是因为据说它模仿了中枢神经系统中自然发生的神经放电模式。事实上，据报道，负责编码来自外周神经元和丘脑的伤害感受方面的神经元以爆冲模式放电。虽然原始突发波形（如De Ridder等人提出和使用的）与中枢神经系统中的神经突发模式之间可能存在重叠，但重要的是要注意，突发参数尚未针对疼痛缓解能力进行优化，因为尚未充分探索参数空间。例如，还没有表征有源与无源电荷恢复的效果差异。除了电荷恢复之外，还有许多其他参数可以改变：爆发间频率、爆发内频率、脉冲宽度、脉冲形状，以及脉冲数。未来的研究需要优化突发编程，并阐明不同爆冲式SCS模式产生的生理变化如何反映在临床前行为和临床中。