Tsaava Téa, Datta-Chaudhuri Timir, Addorisio Meghan E, Masi Emily Battinelli, Silverman Harold A, Newman Justin E, Imperato Gavin H, Bouton Chad, Tracey Kevin J, Chavan Sangeeta S, Chang Eric H
Laboratory of Biomedical Science, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030 USA.
Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, 350 Community Drive, Manhasset, NY 11030 USA.
Bioelectron Med. 2020 Apr 10;6:8. doi: 10.1186/s42234-020-00042-8. eCollection 2020.
Electrical stimulation of peripheral nerves is a widely used technique to treat a variety of conditions including chronic pain, motor impairment, headaches, and epilepsy. Nerve stimulation to achieve efficacious symptomatic relief depends on the proper selection of electrical stimulation parameters to recruit the appropriate fibers within a nerve. Recently, electrical stimulation of the vagus nerve has shown promise for controlling inflammation and clinical trials have demonstrated efficacy for the treatment of inflammatory disorders. This application of vagus nerve stimulation activates the inflammatory reflex, reducing levels of inflammatory cytokines during inflammation.
Here, we wanted to test whether altering the parameters of electrical vagus nerve stimulation would change circulating cytokine levels of normal healthy animals in the absence of increased inflammation. To examine this, we systematically tested a set of electrical stimulation parameters and measured serum cytokine levels in healthy mice.
Surprisingly, we found that specific combinations of pulse width, pulse amplitude, and frequency produced significant increases of the pro-inflammatory cytokine tumor necrosis factor (TNF), while other parameters selectively lowered serum TNF levels, as compared to sham-stimulated mice. In addition, serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) were significantly increased by select parameters of electrical stimulation but remained unchanged with others.
These results indicate that electrical stimulation parameter selection is critically important for the modulation of cytokines via the cervical vagus nerve and that specific cytokines can be increased by electrical stimulation in the absence of inflammation. As the next generation of bioelectronic therapies and devices are developed to capitalize on the neural regulation of inflammation, the selection of nerve stimulation parameters will be a critically important variable for achieving cytokine-specific changes.
外周神经电刺激是一种广泛应用于治疗多种病症的技术，包括慢性疼痛、运动障碍、头痛和癫痫。通过神经刺激实现有效的症状缓解取决于正确选择电刺激参数，以募集神经内合适的纤维。最近，迷走神经电刺激已显示出控制炎症的前景，临床试验也证明了其对炎症性疾病的治疗效果。这种迷走神经刺激的应用激活了炎症反射，在炎症期间降低了炎症细胞因子的水平。
在此，我们想测试在没有炎症增加的情况下，改变迷走神经电刺激参数是否会改变正常健康动物的循环细胞因子水平。为了研究这一点，我们系统地测试了一组电刺激参数，并测量了健康小鼠的血清细胞因子水平。
令人惊讶的是，我们发现与假刺激小鼠相比，脉冲宽度、脉冲幅度和频率的特定组合会导致促炎细胞因子肿瘤坏死因子（TNF）显著增加，而其他参数则选择性地降低血清TNF水平。此外，抗炎细胞因子白细胞介素-10（IL-10）的血清水平在某些电刺激参数下显著增加，但在其他参数下保持不变。
这些结果表明，电刺激参数的选择对于通过颈迷走神经调节细胞因子至关重要，并且在没有炎症的情况下，特定细胞因子可通过电刺激增加。随着下一代生物电子疗法和设备的开发以利用炎症的神经调节作用，神经刺激参数的选择将是实现细胞因子特异性变化的关键重要变量。
