Sagalajev Boriss, Zhang Tianhe, Abdollahi Nooshin, Yousefpour Noosha, Medlock Laura, Al-Basha Dhekra, Ribeiro-da-Silva Alfredo, Esteller Rosana, Ratté Stéphanie, Prescott Steven A
Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Boston Scientific Neuromodulation, Valencia, CA 25155, USA.
Neuron. 2024 Feb 7;112(3):404-420.e6. doi: 10.1016/j.neuron.2023.10.021. Epub 2023 Nov 15.
Electrically activating mechanoreceptive afferents inhibits pain. However, paresthesia evoked by spinal cord stimulation (SCS) at 40-60 Hz becomes uncomfortable at high pulse amplitudes, limiting SCS "dosage." Kilohertz-frequency SCS produces analgesia without paresthesia and is thought, therefore, not to activate afferent axons. We show that paresthesia is absent not because axons do not spike but because they spike asynchronously. In a pain patient, selectively increasing SCS frequency abolished paresthesia and epidurally recorded evoked compound action potentials (ECAPs). Dependence of ECAP amplitude on SCS frequency was reproduced in pigs, rats, and computer simulations and is explained by overdrive desynchronization: spikes desychronize when axons are stimulated faster than their refractory period. Unlike synchronous spikes, asynchronous spikes fail to produce paresthesia because their transmission to somatosensory cortex is blocked by feedforward inhibition. Our results demonstrate how stimulation frequency impacts synchrony based on axon properties and how synchrony impacts sensation based on circuit properties.
电刺激机械感受性传入神经可抑制疼痛。然而，脊髓刺激（SCS）在40 - 60赫兹时诱发的感觉异常在高脉冲幅度下会变得不适，限制了SCS的“剂量”。千赫兹频率的SCS可产生无感觉异常的镇痛作用，因此被认为不会激活传入轴突。我们发现没有感觉异常不是因为轴突不产生动作电位，而是因为它们异步产生动作电位。在一名疼痛患者中，选择性增加SCS频率可消除感觉异常和硬膜外记录的诱发复合动作电位（ECAPs）。在猪、大鼠和计算机模拟中重现了ECAP幅度对SCS频率的依赖性，这可以通过超速去同步化来解释：当轴突受到比其不应期更快的刺激时，动作电位会去同步化。与同步动作电位不同，异步动作电位不会产生感觉异常，因为它们向体感皮层的传导被前馈抑制所阻断。我们的结果证明了刺激频率如何基于轴突特性影响同步性，以及同步性如何基于神经回路特性影响感觉。
