Chronic pain remains a leading cause of disability worldwide, and there is still a clinical reliance on opioids despite the medical side effects associated with their use and societal impacts associated with their abuse. An alternative approach is the use of electrical neuromodulation to produce analgesia. Direct current can block action potential propagation but leads to tissue damage if maintained. We have developed a form of ultra low frequency (ULF) biphasic current and studied its effects. In anesthetized rats, this waveform produced a rapidly developing and completely reversible conduction block in >85% of spinal sensory nerve fibers excited by peripheral stimulation. Sustained ULF currents at lower amplitudes led to a slower onset but reversible conduction block. Similar changes were seen in an animal model of neuropathic pain, where ULF waveforms blocked sensory neuron ectopic activity, known to be an important driver of clinical neuropathic pain. Using a computational model, we showed that prolonged ULF currents could induce accumulation of extracellular potassium, accounting for the slowly developing block observed in rats. Last, we tested the analgesic effects of epidural ULF currents in 20 subjects with chronic leg and back pain. Pain ratings improved by 90% after 2 weeks. One week after explanting the electrodes, pain ratings reverted to 72% of pretreatment screening value. We conclude that epidural spinal ULF neuromodulation represents a promising therapy for treating chronic pain.

慢性疼痛仍然是世界范围内导致残疾的主要原因，尽管阿片类药物的使用会产生医学副作用，并且滥用会产生社会影响，但临床上仍然依赖阿片类药物。另一种方法是使用电神经调节来产生镇痛作用。直流电可以阻止动作电位的传播，但如果维持下去会导致组织损伤。我们开发了一种超低频 (ULF) 双相电流形式并研究了其影响。在麻醉的大鼠中，该波形在由外周刺激激发的 85% 以上的脊髓感觉神经纤维中产生了快速发展且完全可逆的传导阻滞。较低幅度的持续 ULF 电流导致较慢的发作但可逆的传导阻滞。在神经性疼痛的动物模型中也观察到了类似的变化，其中 ULF 波形阻断了感觉神经元异位活动，已知是临床神经性疼痛的重要驱动因素。使用计算模型，我们表明延长的 ULF 电流可以诱导细胞外钾的积累，解释在大鼠中观察到的缓慢发展的阻滞。最后，我们在 20 名患有慢性腿部和背部疼痛的受试者中测试了硬膜外 ULF 电流的镇痛效果。两周后疼痛评分提高了 90%。取出电极一周后，疼痛评分恢复到治疗前筛查值的 72%。我们得出结论，硬膜外脊髓 ULF 神经调节代表了治疗慢性疼痛的有前途的疗法。我们发现延长的 ULF 电流可以诱导细胞外钾的积累，这解释了在大鼠中观察到的缓慢发展的阻滞。最后，我们在 20 名患有慢性腿部和背部疼痛的受试者中测试了硬膜外 ULF 电流的镇痛效果。两周后疼痛评分提高了 90%。取出电极一周后，疼痛评分恢复到治疗前筛查值的 72%。我们得出结论，硬膜外脊髓 ULF 神经调节代表了治疗慢性疼痛的有前途的疗法。我们发现延长的 ULF 电流可以诱导细胞外钾的积累，这解释了在大鼠中观察到的缓慢发展的阻滞。最后，我们在 20 名患有慢性腿部和背部疼痛的受试者中测试了硬膜外 ULF 电流的镇痛效果。两周后疼痛评分提高了 90%。取出电极一周后，疼痛评分恢复到治疗前筛查值的 72%。我们得出结论，硬膜外脊髓 ULF 神经调节代表了治疗慢性疼痛的有前途的疗法。疼痛评分恢复到治疗前筛查值的 72%。我们得出结论，硬膜外脊髓 ULF 神经调节代表了治疗慢性疼痛的有前途的疗法。疼痛评分恢复到治疗前筛查值的 72%。我们得出结论，硬膜外脊髓 ULF 神经调节代表了治疗慢性疼痛的有前途的疗法。