Program in Physical Therapy, Washington University School of Medicine, 4444 Forest Park Avenue, Suite 1101, St. Louis, MO 63108, United States of America.
Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, United States of America.
J Neural Eng. 2022 Oct 31;19(5). doi: 10.1088/1741-2552/ac9a00.
. Spinal cord injury (SCI) often results in debilitating movement impairments and neuropathic pain. Electrical stimulation of spinal neurons holds considerable promise both for enhancing neural transmission in weakened motor pathways and for reducing neural transmission in overactive nociceptive pathways. However, spinal stimulation paradigms currently under development for individuals living with SCI continue overwhelmingly to be developed in the context of motor rehabilitation alone. The objective of this study is to test the hypothesis that motor-targeted spinal stimulation simultaneously modulates spinal nociceptive transmission.. We characterized the neuromodulatory actions of motor-targeted intraspinal microstimulation (ISMS) on the firing dynamics of large populations of discrete nociceptive specific and wide dynamic range (WDR) neurons. Neurons were accessed via dense microelectrode arrays implantedinto lumbar enlargement of rats. Nociceptive and non-nociceptive cutaneous transmission was induced before, during, and after ISMS by mechanically probing the L5 dermatome.. Our primary findings are that (a) sub-motor threshold ISMS delivered to spinal motor pools immediately modulates concurrent nociceptive transmission; (b) the magnitude of anti-nociceptive effects increases with longer durations of ISMS, including robust carryover effects; (c) the majority of all identified nociceptive-specific and WDR neurons exhibit firing rate reductions after only 10 min of ISMS; and (d) ISMS does not increase spinal responsiveness to non-nociceptive cutaneous transmission. These results lead to the conclusion that ISMS parameterized to enhance motor output results in an overall net decrease n spinal nociceptive transmission.. These results suggest that ISMS may hold translational potential for neuropathic pain-related applications and that it may be uniquely suited to delivering multi-modal therapeutic benefits for individuals living with SCI.
脊髓损伤(SCI)常导致运动功能受损和神经病理性疼痛。脊髓神经元的电刺激在增强减弱的运动通路中的神经传递和减少过度活跃的伤害性通路中的神经传递方面具有很大的潜力。然而,目前为 SCI 患者开发的脊髓刺激方案绝大多数仍然仅在运动康复的背景下进行开发。本研究的目的是检验这样一个假设,即针对运动的脊髓刺激同时调节脊髓伤害性传递。我们描述了针对运动的脊髓内微刺激(ISMS)对离散伤害性特异性和宽动态范围(WDR)神经元的大群体的放电动力学的神经调节作用。神经元通过植入大鼠腰椎扩大部的密集微电极阵列来访问。在 ISMS 之前、期间和之后,通过机械探测 L5 皮区来诱导伤害性和非伤害性皮肤传递。我们的主要发现是:(a)施加于脊髓运动池的亚运动阈值 ISMS 立即调节并发的伤害性传递;(b)ISMS 持续时间越长,抗伤害性作用的幅度越大,包括强大的持续效应;(c)仅 10 分钟的 ISMS 后,大多数已识别的伤害性特异性和 WDR 神经元的放电率均降低;(d)ISMS 不会增加对非伤害性皮肤传递的脊髓反应性。这些结果得出结论,针对增强运动输出的 ISMS 参数化导致脊髓伤害性传递的整体净减少。这些结果表明,ISMS 可能具有转化为神经病理性疼痛相关应用的潜力,并且它可能特别适合为 SCI 患者提供多模式治疗益处。