Safe Direct Current Stimulator (SDCS) technology for blocking chronicperipheral pain

项目摘要 该项目的中心目标是推进治疗应用和使用离子 直流电与神经系统相互作用。直流电（DC）与双相电荷平衡相比 通常由神经假体用于与神经系统接口的脉冲可以更自然地控制神经系统， 活动与用于兴奋神经元的双相电流脉冲不同，DC可以兴奋，抑制和调节敏感性 的神经元。虽然DC可以在短时间内用于与神经系统相互作用，但长期使用这种药物可能会导致神经系统损伤。 由于DC的固有特性，用于可植入假体应用的刺激范例是不可能的。 违反了金属电极界面处的电荷注入安全约束。新技术，安全直达 电流刺激（SDCS）克服了这些限制，并开辟了另一条研究途径， 令人兴奋的可能性，使用直流电接口的神经系统。 我们将优化离子DC的使用，以改善慢性疼痛抑制的性能。慢性 疼痛抑制需要抑制携带疼痛的神经元传导动作电位。我们获得 麻醉大鼠模型的初步数据显示，坐骨神经处的安全DC神经阻滞可以 抑制疼痛信号传播到脊髓，但允许感觉和肌肉的正常传播 运动 在这里，我们建议通过以下方式来理解疼痛信号的安全DC调制背后的机制： 麻醉的小鼠和大鼠实验。我们将进行行为实验，以了解 本发明的目的是为了证实该技术用于解决清醒动物中的慢性疼痛的有效性。我们还将进行组织学 研究，以调查治疗的生物学影响。最后，我们将推进SDCS技术， 识别和解决小型化和植入式SDCS的关键技术挑战。 目标1。检查iDC抑制伤害性疼痛的作用机制。 目标2.检查iDC对神经病理性疼痛信号的影响和潜在机制。 目标3。研究iDC抑制神经性疼痛的行为实验。 目标4。植入式SDCS技术开发。

Project Summary The central goal of this project is to advance the therapeutic applications and the potential for using ionic direct current to interact with the nervous system. Direct current (DC) compared to biphasic charge balanced pulses normally used by neural prostheses to interface to the nervous system, can more naturally control neural activity. Unlike biphasic current pulses used to excite neurons, DC can excite, inhibit, and modulate sensitivity of neurons. While DC can be used for short durations to interact with the nervous system, chronic use of this stimulation paradigm for implantable prosthetic applications has not been possible due to the DC’s inherent violation of the charge injection safety constraints at the metal electrode interfaces. New technology, safe direct current stimulation (SDCS) overcomes these constraints and opens an additional avenue for research into exciting possibilities of using DC to interface to the nervous system. We will optimize the use of ionic DC to improve the performance of chronic pain suppression. Chronic pain suppression requires inhibiting pain carrying neurons from conducting action potentials. We obtained preliminary data in an anesthetized rat model showing that safe DC neural block at the sciatic nerve could suppress pain signals from propagating to the spinal cord, but allow normal propagation of sensation and muscle movement. Here we propose to understand the mechanism behind safe DC modulation of pain signals through anesthetized mouse and rat experiments. We will conduct the behavioral experiments to understand the effectiveness of this technology for addressing chronic pain in an awake animal. We will also conduct histological studies to investigate the biological impact of the therapy. Finally, we will advance the SDCS technology by identifying and solving the key technical challenges with a miniaturized and implantable SDCS. Aim 1. Examine the mechanism of the iDC effect on suppression of nociceptive pain. Aim 2. Examine the effects and underlying mechanisms of iDC on neuropathic pain signals. Aim 3. Behavioral experiments to study iDC for inhibition of neuropathic pain. Aim 4. Implantable SDCS technology development.