Modulation of activity and conduction in single dorsal column axons by kilohertz-frequency spinal cord stimulation
Modulation of activity and conduction in single dorsal column axons by kilohertz-frequency spinal cord stimulation
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DOI：
10.1152/jn.00701.2016
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发表时间：
2017-01-01
影响因子：
2.5
通讯作者：
Grill, Warren M.
中科院分区：
文献类型：
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作者：
Crosby, Nathan D.;Janik, John J.;Grill, Warren M.
千赫兹频率脊髓刺激（KHF-SCS）是一种潜在的无感觉异常治疗慢性疼痛的方法。然而，KHF-SCS 对脊柱背柱 (DC) 轴突的影响及其作用机制仍不清楚。本研究的目的是量化 KHF-SCS 在一系列频率（1、5、10 或 20 kHz）和波形（双相脉冲或正弦曲线）内对 DC 轴突的激活和传导阻滞。定制铂电极将 SCS 递送至麻醉的雄性 Sprague-Dawley 大鼠的 T10/T11 背柱。在 KHF-SCS 过程中记录单个 DC 轴突和复合动作电位，以评估 SCS 诱发的活动。 DC 轴突对 KHF-SCS 的反应包括短暂的起始放电、缓慢适应异步放电和传导阻滞。 KHF-SCS 的影响大多发生在远高于运动阈值的情况下，但孤立的单位被激活的幅度显示会降低大鼠的行为敏感性。 SCS 引起的活动在一系列频率 (5-20 kHz) 和波形（双相和正弦）上相似。 1kHz SCS 的刺激会引起更多的轴突放电，这些放电也与 SCS 波形更加相位同步，但仅限于高于运动阈值的幅度。这些数据定量地描述了可能调节疼痛感知和感觉异常的中枢神经系统活动，从而为继续研究 KHF-SCS 的机制及其作为慢性疼痛疗法的优化奠定了基础。鉴于 DC 活动的异步和瞬态性质，传统 SCS 的相同机制（即持续、周期性 DC 激活）不太可能适用于 KHF-SCS。新的和值得注意的千赫兹频率脊髓刺激 (KHF-SCS) 是一种新的 SCS 模式，可能比传统 SCS 提供更好的疼痛缓解效果。然而，其作用机制尚不清楚，特别是刺激对背柱 (DC) 轴突的影响，而背柱 (DC) 轴突是刺激的主要目标。这项研究提供了 KHF-SCS 期间单个 DC 轴突的首次记录，以量化有可能介导 KHF-SCS 镇痛作用的 DC 活动。
Kilohertz-frequency spinal cord stimulation (KHF-SCS) is a potential paresthe-sia-free treatment for chronic pain. However, the effects of KHF-SCS on spinal dorsal column (DC) axons and its mechanisms of action remain unknown. The objectives of this study were to quantify activation and conduction block of DC axons by KHF-SCS across a range of frequencies (1, 5, 10, or 20 kHz) and waveforms (biphasic pulses or sinusoids). Custom platinum electrodes delivered SCS to the T10/T11 dorsal columns of anesthetized male Sprague-Dawley rats. Single DC axons and compound action potentials were recorded during KHF-SCS to evaluate SCS-evoked activity. Responses to KHF-SCS in DC axons included brief onset firing, slowly accommodating asynchronous firing, and conduction block. The effects of KHF-SCS mostly occurred well above motor thresholds, but isolated units were activated at amplitudes shown to reduce behavioral sensitivity in rats. Activity evoked by SCS was similar across a range of frequencies (5-20 kHz) and waveforms (biphasic and sinusoidal). Stimulation at 1-kHz SCS evoked more axonal firing that was also more phase-synchronized to the SCS waveform, but only at amplitudes above motor threshold. These data quantitatively characterize the central nervous system activity that may modulate pain perception and paresthesia, and thereby provide a foundation for continued investigation of the mechanisms of KHF-SCS and its optimization as a therapy for chronic pain. Given the asynchronous and transient nature of DC activity, it is unlikely that the same mechanisms underlying conventional SCS (i.e., persistent, periodic DC activation) apply to KHF-SCS.NEW & NOTEWORTHY Kilohertz-frequency spinal cord stimulation (KHF-SCS) is a new mode of SCS that may offer better pain relief than conventional SCS. However, the mechanism of action is poorly characterized, especially the effects of stimulation on dorsal column (DC) axons, which are the primary target of stimulation. This study provides the first recordings of single DC axons during KHF-SCS to quantify DC activity that has the potential to mediate the analgesic effects of KHF-SCS.