脊髓刺激(SCS)对慢性疼痛的神经生理作用知之甚少,导致效率低下,易于失败的编程协议和疼痛缓解不足。尽管如此,新的刺激模式在临床上定期引入和采用。传统上,感觉异常被认为是缓解疼痛所必需的,尽管新颖的范例提供镇痛而没有感觉异常。然而,像缓解疼痛,SCS引起的感觉异常的神经生理学基础尚不清楚。这里,我们将生物物理模型与临床感觉异常阈值(两性)配对,以研究刺激频率如何影响与感觉异常和镇痛相关的SCS的神经反应.具体来说,我们对背柱(DC)轴突反应进行了建模,背柱核(DCN)突触传递,直流光纤侧支内的传导故障,和背角网络输出。重要的是,我们发现高频刺激会降低DC纤维激活阈值,这反过来准确地预测临床感觉异常感知阈值。此外,我们表明,高频SCS产生异步直流光纤尖峰和最终异步DCN输出,提供了一个合理的生物物理基础,说明为什么高频SCS比低频刺激不太舒适,并且产生质量上不同的感觉。最后,我们证明了模型背角网络输出对尖峰定时的SCS固有变化敏感,这可能有助于患者之间的异质性疼痛缓解。重要的是,我们表明,模型直流纤维络脉不能可靠地跟随高频刺激,强烈影响网络输出,通常在高频产生抗伤害性作用。总之,这些发现阐明了SCS如何影响神经系统,并提供了对感觉异常产生和疼痛缓解的生物物理学的见解.意义声明脊髓刺激(SCS)对神经系统的影响知之甚少,导致临床成功率不足。这里,我们使用生物物理建模方法来研究SCS的神经反应。我们证明了低频和高频刺激在背柱中产生相反的反应,脑干,和背角。重要的是,我们的建模方法能够准确地预测临床感觉异常阈值作为频率的函数,并为频率依赖性效应对感觉异常质量和疼痛缓解提供合理的生物物理解释。总的来说,我们的结果大大增强了我们对SCS的神经反应的理解,从而为解释临床观察和未来SCS系统开发的关键见解提供了背景。
The neurophysiological effects of spinal cord stimulation (SCS) for chronic pain are poorly understood, resulting in inefficient failure-prone programming protocols and inadequate pain relief. Nonetheless, novel stimulation patterns are regularly introduced and adopted clinically. Traditionally, paresthetic sensation is considered necessary for pain relief, although novel paradigms provide analgesia without paresthesia. However, like pain relief, the neurophysiological underpinnings of SCS-induced paresthesia are unknown. Here, we paired biophysical modeling with clinical paresthesia thresholds (of both sexes) to investigate how stimulation frequency affects the neural response to SCS relevant to paresthesia and analgesia. Specifically, we modeled the dorsal column (DC) axonal response, dorsal column nucleus (DCN) synaptic transmission, conduction failure within DC fiber collaterals, and dorsal horn network output. Importantly, we found that high-frequency stimulation reduces DC fiber activation thresholds, which in turn accurately predicts clinical paresthesia perception thresholds. Furthermore, we show that high-frequency SCS produces asynchronous DC fiber spiking and ultimately asynchronous DCN output, offering a plausible biophysical basis for why high-frequency SCS is less comfortable and produces qualitatively different sensation than low-frequency stimulation. Finally, we demonstrate that the model dorsal horn network output is sensitive to SCS-inherent variations in spike timing, which could contribute to heterogeneous pain relief across patients. Importantly, we show that model DC fiber collaterals cannot reliably follow high-frequency stimulation, strongly affecting the network output and typically producing antinociceptive effects at high frequencies. Altogether, these findings clarify how SCS affects the nervous system and provide insight into the biophysics of paresthesia generation and pain relief.