Objective. Electrical neuromodulation is an established non-pharmacological treatment for chronic pain. However, existing devices using pulsatile stimulation typically inhibit pain pathways indirectly and are not suitable for all types of chronic pain. Direct current (DC) stimulation is a recently developed technology which affects small-diameter fibres more strongly than pulsatile stimulation. Since nociceptors are predominantly small-diameter Aδ and C fibres, we investigated if this property could be applied to preferentially reduce nociceptive signalling. Approach. We applied a DC waveform to the sciatic nerve in rats of both sexes and recorded multi-unit spinal activity evoked at the hindpaw using various natural stimuli corresponding to different sensory modalities rather than broad-spectrum electrical stimulus. To determine if DC neuromodulation is effective across different types of chronic pain, tests were performed in models of neuropathic and inflammatory pain. Main results. We found that in both pain models tested, DC application reduced responses evoked by noxious stimuli, as well as tactile-evoked responses which we suggest may be involved in allodynia. Different spinal activity of different modalities were reduced in naïve animals compared to the pain models, indicating that physiological changes such as those mediated by disease states could play a larger role than previously thought in determining neuromodulation outcomes. Significance. Our findings support the continued development of DC neuromodulation as a method for reduction of nociceptive signalling, and suggests that it may be effective at treating a broader range of aberrant pain conditions than existing devices.

中文翻译：

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外周直流电可减少啮齿动物疼痛模型中脊髓自然诱发的伤害性活动

客观的。电神经调节是一种成熟的慢性疼痛非药物治疗方法。然而，现有的使用脉动刺激的装置通常间接抑制疼痛通路，并不适合所有类型的慢性疼痛。直流 (DC) 刺激是一项最近开发的技术，它比脉动刺激对小直径纤维的影响更大。由于伤害感受器主要是小直径 Aδ 和 C 纤维，我们研究了是否可以应用此特性来优先减少伤害感受信号。方法。我们对两性大鼠的坐骨神经应用直流波形，并使用与不同感觉方式相对应的各种自然刺激而不是广谱电刺激来记录后爪诱发的多单位脊髓活动。为了确定 DC 神经调节是否对不同类型的慢性疼痛有效，在神经性疼痛和炎性疼痛模型中进行了测试。主要结果。我们发现，在测试的两种疼痛模型中，直流电应用减少了由有害刺激引起的反应，以及我们认为可能与异常性疼痛有关的触觉诱发反应。与疼痛模型相比，幼稚动物中不同方式的不同脊柱活动有所减少，这表明诸如疾病状态介导的生理变化在决定神经调节结果方面可能发挥比以前认为的更大的作用。意义。我们的研究结果支持 DC 神经调节作为一种减少伤害性信号传导的方法的持续发展，并表明它可能比现有设备更有效地治疗更广泛的异常疼痛状况。