【原】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（三）

 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。

2.2. Tonic spinal cord stimulation and suprasegmental mechanisms

Once activated, supraspinal cell regions are known to modulate the incoming nociceptive signals at the spinal level through descending fiber projections. Brainstem nuclei such as the locus coeruleus and the nucleus raphe magnus, but also the rostral ventromedial medulla, are activated by Tonic SCS and in turn modulate the spinal nociceptive signal (Fig. 1). The descending projections release a variety of neurotransmitters including serotonin (5-HT), which exerts an inhibitory effect (based on the receptor involved) on the incoming nociceptive fibers, and this maintains long-term neuropathic pain. Further detailed research on the spinal 5-HT receptors that contribute to the pain-relieving effects of Tonic SCS in chronic neuropathic rats was performed, and with use of intrathecal application of antagonists and agonists for the various serotonin receptors, it was shown that the activation of the 5HT-3 receptor seems to operate through spinal GABAergic interneurons.

2.2.传统SCS和脊髓上水平机制

一旦激活，脊髓上细胞区域通过下行纤维投射在脊髓水平调节传入的伤害性信号。脑干核团，如蓝斑和中缝大核，以及延髓头端腹内侧核，被传统SCS激活，进而调节脊髓伤害性信号。下行投射释放多种神经递质，包括5-羟色胺（5-HT），它对传入的伤害性纤维产生抑制作用（基于所涉及的受体），从而维持长期的神经病理性疼痛。对脊髓5-HT受体进行了进一步的详细研究，该受体有助于慢性神经病理性疼痛大鼠中传统SCS的镇痛作用，并通过鞘内应用各种5-羟色胺受体的拮抗剂和激动剂，表明5HT-3受体的激活似乎通过脊髓GABA能中间神经元进行。

First evidence for a role of suprasegmental mechanisms underlying Tonic SCS was presented by El-Khoury et al., who demonstrated that Tonic SCS of the dorsal column nuclei reduces allodynia and hypersensitivity in an experimental model of chronic neuropathic pain, even after dorsal column transection below these nuclei. From this, it was suggested that the observed inhibition in terms of allodynia and hypersensitivity responses can be attributed to the activation of brainstem pain-modulating centers through rostral projections of the dorsal column nuclei.

El Khoury等人首次提出了传统SCS脊髓上水平机制作用的证据，他们证明，在慢性神经病理性疼痛的实验模型中，即使在这些核下的背柱横断后，背柱核的传统SCS依然可以降低异常痛觉和超敏反应。由此，有人提出，所观察到的异常疼痛和超敏反应抑制可归因于通过背柱核的吻侧投射激活脑干疼痛调节中心。

That Tonic SCS can also modulate activation patterns in brain areas at subcortical and cortical levels has been shown in a rodent model of chronic neuropathic pain. How Tonic SCS alters cortical processing has also been shown by clinical studies using imaging approaches such as functional magnetic resonance imaging (fMRI), positron-emission tomography, single-photon emission computed tomography, and 133-Xe inhalation (reviewed in Bentley et al.). These cortical changes during Tonic SCS may represent direct effects from dorsal column stimulation or inhibition of nociceptive signals arising from the periphery, or they may reflect complex modulatory effects on somatosensory and affective processing. Early clinical fMRI work on the supraspinal effects of Tonic SCS has demonstrated modulation of brain regions associated with the lateral spinothalamic tract (l-STT). The l-STT is responsible for the transmission of pain aspects such as the intensity and location of the painful stimulus. This l-STT pathway projects from the dorsal horn, through the thalamus, to cortical areas such as the somatosensory cortex. An fMRI study performed in 8 patients receiving Tonic SCS demonstrated that this type of stimulation of the dorsal columns increased blood–oxygen level-dependent signals in somatosensory cortices, the sensorimotor cortex, and the insula. Furthermore, a more recent fMRI study with 20 patients, who received Tonic SCS as treatment for FBSS, reported deactivation of the bilateral medial thalamus and its connections to the rostral and caudal cingulate cortex, and the insula. In conclusion, over the years, literature on Tonic SCS has provided evidence for a mechanism of action through both spinal and supraspinal levels.

在慢性神经病理性疼痛的啮齿动物模型中显示，传统SCS还可以调节皮层下和皮层水平的脑区激活模式。使用成像方法的临床研究也显示了传统SCS如何改变皮层处理，如功能磁共振成像（fMRI）、正电子发射断层成像、单光子发射计算机断层成像和133氙吸入。传统SCS期间的这些皮质变化可能代表来自外周的伤害性信号的背柱刺激或抑制的直接效应，或者它们可能反映了对体感和情感处理的复杂调节效应。关于传统SCS的脊髓上效应的早期临床功能磁共振成像研究表明，与脊髓丘脑外侧束（I-STT）相关的脑区受到调节I-STT负责疼痛方面的传递，如疼痛刺激的强度和位置。该I-STT通路从背角通过丘脑投射到皮层区域，如体感皮层。对8名接受传统SCS的患者进行的功能磁共振成像研究表明，这种对背柱的刺激增加了体感皮层、感觉运动皮层和脑岛的血氧水平依赖性信号。此外，最近对20名接受传统SCS治疗的患者进行的功能磁共振成像研究报告，双侧内侧丘脑及其与扣带回头侧和尾侧皮质以及脑岛的连接失活。总之，多年来，关于传统SCS的文献为脊髓和脊髓上水平的作用机制提供了证据。