Bandres Maria F, Gomes Jefferson L, McPherson Jacob Graves
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA.
Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO 63108, USA.
Brain Commun. 2024 Aug 19;6(5):fcae280. doi: 10.1093/braincomms/fcae280. eCollection 2024.
Electrical stimulation of spinal networks below a spinal cord injury is a promising approach to restore functions compromised by inadequate and/or inappropriate neural drive. The most translationally successful examples are paradigms intended to increase neural transmission in weakened yet spared descending motor pathways and spinal motoneurons 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 spinal cord injury. Debilitating spasms, spasticity and neuropathic pain are all common manifestations of hyperexcitable spinal responses to sensory feedback. Whereas spasms and spasticity can often be managed pharmacologically, spinal cord injury-related neuropathic pain is notoriously medically refractory. Interestingly, however, spinal stimulation is a clinically available option for ameliorating neuropathic pain arising from aetiologies other than spinal cord injury, and the limited evidence available to date suggests that it holds considerable promise for reducing spinal cord injury-related neuropathic pain, as well. Spinal stimulation for pain amelioration has traditionally been assumed to modulate sensorimotor networks overlapping with those engaged by spinal stimulation for rehabilitation of movement impairments. Thus, we hypothesize that spinal stimulation intended to increase the ability to move voluntarily may simultaneously reduce transmission in spinal pain pathways. To test this hypothesis, we coupled a rat model of incomplete thoracic spinal cord injury, which results in moderate to severe bilateral movement impairments and spinal cord injury-related neuropathic pain, with electrophysiological measures of neural transmission in networks of spinal neurons integral to the development and persistence of the neuropathic pain state. We find that when intraspinal microstimulation is delivered to the ventral horn with the intent of enhancing voluntary movement, transmission through nociceptive specific and wide dynamic range neurons is significantly depressed in response to pain-related sensory feedback. By comparison, spinal responsiveness to non-pain-related sensory feedback is largely preserved. 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 spinal cord injury.
对脊髓损伤平面以下的脊髓网络进行电刺激是一种很有前景的方法，可用于恢复因神经驱动不足和/或不适当而受损的功能。最具转化成功性的例子是旨在增强减弱但尚存的下行运动通路以及因损伤而与输入切断联系后处于休眠状态的脊髓运动神经元中的神经传递的范例。对于脊髓刺激是否也能够减少因脊髓损伤而病理性过度活跃的通路中的神经传递，人们了解得较少。使人衰弱的痉挛、痉挛状态和神经性疼痛都是脊髓对感觉反馈过度兴奋反应的常见表现。虽然痉挛和痉挛状态通常可以通过药物治疗，但与脊髓损伤相关的神经性疼痛在医学上 notoriously 难治。然而，有趣的是，脊髓刺激是改善脊髓损伤以外病因引起的神经性疼痛的一种临床可用选择，而且迄今为止有限的证据表明，它对于减轻与脊髓损伤相关的神经性疼痛也有很大希望。传统上认为，用于减轻疼痛的脊髓刺激会调节与用于运动障碍康复的脊髓刺激所涉及的感觉运动网络重叠的网络。因此，我们假设，旨在提高自主运动能力的脊髓刺激可能同时减少脊髓疼痛通路中的传递。为了验证这一假设，我们将一种不完全性胸段脊髓损伤的大鼠模型（该模型会导致中度至重度双侧运动障碍以及与脊髓损伤相关的神经性疼痛）与对神经性疼痛状态的发展和持续至关重要的脊髓神经元网络中的神经传递的电生理测量相结合。我们发现，当将脊髓内微刺激施加到腹角以增强自主运动时，在对疼痛相关的感觉反馈作出反应时，通过伤害性特异性和广动力范围神经元的传递会显著降低。相比之下，脊髓对非疼痛相关感觉反馈的反应性在很大程度上得以保留。这些结果表明，可以有意设计脊髓刺激范例以提供多模式治疗益处，直接解决脊髓损伤患者多样化、交叉的康复目标。
