Developing Novel Direct Current Stimulation Technology for Safe Precision Pain Treatment

神经电调节是治疗顽固性慢性疼痛的重要策略 为了药物治疗。然而，目前可用的神经刺激疼痛疗法与有限的 疗效和副作用。我们创造了新型安全的直流电刺激(SDCS)，使植入性 使用离子直流电(IDC)安全地调节神经元活动的神经电子假体。我们的 初步研究提供了令人振奋的证据：将IDC应用于周围神经可诱导有效和 疼痛通路中神经活动的可逆性抑制。有趣的是，IDC可能会被优化为优先 抑制“疼痛”信号，同时允许其他神经信号通过。我们研究的中心目标是发现 神经生理机制，优化刺激参数，建立实验框架 推进用于精确疼痛治疗的新型SDCS神经电子假体的开发。在……里面 目的1，我们将研究IDC如何调节不同亚型传入的传导和兴奋性 神经病理性疼痛大鼠模型中的感觉神经元。通过记录复合动作电位和脑电活动 我们将确定如何以一种方式优化IDC的极性、强度和持续时间 优先抑制“疼痛”信号在外周神经系统的传播。在目标2中，我们将 通过IDC揭示抑制疼痛的脊髓神经生理学机制。具体地说，我们将记录本地字段 检查IDC是否以不同方式影响感觉传入的脊髓传递 伤害性C纤维和非伤害性Aβ纤维。将使用单单元记录来进一步确定如何 IDC影响个体痛处理背角神经元对外周刺激的反应。如果IDC诱导 神经元兴奋，我们将确定是否可以通过使用多极和相控阵IDC来减少兴奋 范例。在目标3中，我们将进行动物行为学测试，以优化疼痛表现的抑制 并检查潜在的副作用。组织学和免疫细胞化学研究将用于评估 IDC短期和长期使用的生物安全性。迫切需要新的非药物治疗策略 慢性疼痛的治疗，以及SDCs在生物系统中的性能刚刚被探索。我们的 这些发现将有助于将SDCS技术用于精确疼痛抑制的生物学基础概念化。基座 关于IDC机制，我们的发现将为Testable的开发提供理论基础和关键见解 以SDCS为基础的“电针”，可能会彻底改变目前治疗慢性疼痛的方法。

Electrical neuromodulation is an important strategy for treating chronic pain conditions that are refractory to pharmacotherapies. However, currently available neurostimulation pain therapies are associated with limited efficacy and side effects. We created novel Safe Direct Current Stimulation (SDCS) that enables implantable neuroelectronic prostheses to safely modulate neuronal activity by using ionic direct current (iDC). Our preliminary studies provide promising evidence that iDC applied at peripheral nerves induces effective and reversible inhibition of neural activity in pain pathways. Intriguingly, iDC may be optimized to preferentially inhibit “pain” signals, while allowing the other nerve signals to pass. The central goal of our study is to uncover neurophysiologic mechanisms, optimize stimulation parameters, and establish the experimental framework for advancing the development of novel SDCS-based neuroelectronic prostheses for precision pain treatment. In Aim 1, we will examine how iDC modulates the conduction and excitability of different subtypes of afferent sensory neurons in a rat model of neuropathic pain. By recording compound action potentials and activity in teased nerve fibers, we will determine how to optimize the polarity, intensity, and duration of iDC in a way that preferentially suppresses propagation of “pain” signals in the peripheral nervous system. In Aim 2, we will uncover spinal neurophysiologic mechanisms for pain inhibition by iDC. Specifically, we will record local field potential in dorsal horn to examine if iDC differentially affects spinal transmission of sensory inputs from nociceptive C-fibers and non-nociceptive Aβ-fibers. Single-unit recording will be used to further determine how iDC affects responses of individual pain-processing dorsal horn neurons to peripheral stimuli. If iDC induces neuronal excitation, we will determine if the excitation can be reduced by using multipolar and phasic-array iDC paradigms. In Aim 3, we will conduct animal behavior tests to optimize the suppression of pain manifestations by iDC and examine potential side effects. Histologic and immunocytochemical studies will be used to evaluate the biosafety of iDC with short- and long-term use. Novel non-pharmacologic strategies are greatly needed for chronic pain treatment, and the performance of SDCS in biological systems is just now being explored. Our findings will help to conceptualize the biological basis of SDCS techniques for precision pain inhibition. Based on iDC mechanisms, our findings will provide rationales and critical insights for the development of testable SDCS-based “electroceuticals” that may revolutionize current approaches to chronic pain treatment.