Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury.
Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury.
复制标题
以运动为目标的脊髓刺激促进慢性脊髓损伤中病理性伤害性传递的同时重新平衡。
DOI：
10.1101/2023.04.12.536477
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
McPherson,JacobG
中科院分区：
文献类型：
--
作者：
Bandres,MariaF;Gomes,JeffersonL;McPherson,JacobG
电刺激脊髓损伤（SCI）下的脊髓网络是一种很有前途的方法，以恢复受损的兴奋性神经驱动不足的功能。最成功的例子是旨在增加神经传递的范式，这些范式是在被削弱但幸免于难的运动通路和脊髓运动网络中进行的，脊髓运动网络在被损伤从其输入切断后处于休眠状态。尚不清楚的是，脊髓刺激是否也能够减少因SCI而病理性过度活跃的通路中的神经传递。衰弱性痉挛、痉挛状态和神经性疼痛都是对感觉反馈的过度兴奋性脊髓反应的常见表现。但是，尽管痉挛和痉挛状态通常可以通过药物治疗，但SCI相关的神经性疼痛在医学上是众所周知的难治性。然而，有趣的是，脊髓刺激是一种临床上可用于改善由SCI以外的病因引起的神经性疼痛的选择，并且传统上认为它调节与脊髓刺激参与的运动康复重叠的感觉运动网络。因此，我们推断旨在增加运动通路中的传输的脊髓刺激可以同时减少脊髓疼痛通路中的传输。使用一个经过充分验证的SCI临床前模型，导致严重的双侧运动障碍和SCI相关的神经性疼痛，我们表明，神经元的反应性神经性疼痛状态的发展和持续性不可或缺的运动靶向脊髓刺激，同时保留脊髓反应非疼痛相关的感觉反馈。这些结果表明，脊髓刺激范例可以被有意地设计为提供多模式的治疗益处，直接解决SCI患者的多样化，交叉康复目标。
Electrical stimulation of spinal networks below a spinal cord injury (SCI) is a promising approach to restore functions compromised by inadequate excitatory neural drive. The most translationally successful examples are paradigms intended to increase neural transmission in weakened yet spared motor pathways and spinal motor networks rendered dormant after being severed from their inputs by lesion. Less well understood is whether spinal stimulation is also capable of reducing neural transmission in pathways made pathologically overactive by SCI. Debilitating spasms, spasticity, and neuropathic pain are all common manifestations of hyperexcitable spinal responses to sensory feedback. But whereas spasms and spasticity can often be managed pharmacologically, SCI-related neuropathic pain is notoriously medically refractory. Interestingly, however, spinal stimulation is a clinically available option for ameliorating neuropathic pain arising from etiologies other than SCI, and it has traditionally been assumed to modulate sensorimotor networks overlapping with those engaged by spinal stimulation for motor rehabilitation. Thus, we reasoned that spinal stimulation intended to increase transmission in motor pathways may simultaneously reduce transmission in spinal pain pathways. Using a well-validated pre-clinical model of SCI that results in severe bilateral motor impairments and SCI-related neuropathic pain, we show that the responsiveness of neurons integral to the development and persistence of the neuropathic pain state can be enduringly reduced by motor-targeted spinal stimulation while preserving spinal responses to non-pain-related sensory feedback. These results suggest that spinal stimulation paradigms could be intentionally designed to afford multi-modal therapeutic benefits, directly addressing the diverse, intersectional rehabilitation goals of people living with SCI.