Abstract：
Spasticity is a complex and multidimensional disorder that impacts nearly 75% of individuals with spinal cord injury (SCI) and currently lacks adequate treatment options. This sensorimotor condition is burdensome as hyperexcitability of reflex pathways result in exacerbated reflex responses, co-contractions of antagonistic muscles, and involuntary movements. Transcutaneous spinal cord stimulation (tSCS) has become a popular tool in the human SCI research field. The likeliness for this intervention to be successful as a noninvasive anti-spastic therapy after SCI is suggested by a mild and transitory improvement in spastic symptoms following a single stimulation session, but it remains to be determined if repeated tSCS over the course of weeks can produce more profound effects. Despite its popularity, the neuroplasticity induced by tSCS also remains widely unexplored, particularly due to the lack of suitable animal models to investigate this intervention. Thus, the basis of this work was to use tSCS over multiple sessions (multi-session tSCS) in a rat model to target spasticity after SCI and identify the long-term physiological improvements and anatomical neuroplasticity occurring in the spinal cord. Here, we show that multi-session tSCS in rats with an incomplete (severe T9 contusion) SCI (1) decreases hyperreflexia, (2) increases the low frequency-dependent modulation of the H-reflex, (3) prevents potassium-chloride cotransporter isoform 2 (KCC2) membrane downregulation in lumbar motoneurons, and (4) generally augments motor output, i.e., EMG amplitude in response to single pulses of tSCS, particularly in extensor muscles. Together, this work displays that multi-session tSCS can target and diminish spasticity after SCI as an alternative to pharmacological interventions and begins to highlight the underlying neuroplasticity contributing to its success in improving functional recovery.
摘要：
痉挛是一种复杂的多维疾病，影响了近75％的脊髓损伤（SCI）患者，目前缺乏足够的治疗选择。这种感觉运动状况是繁重的，因为反射途径的过度兴奋会导致反射反应加剧，拮抗肌肉的共同收缩，和非自愿的运动。经皮脊髓刺激（tSCS）已成为人类SCI研究领域的热门工具。这种干预作为SCI后的非侵入性抗痉挛治疗成功的可能性在于单次刺激后痉挛症状的轻度和短暂改善。但在几周内重复tSCS是否会产生更深远的影响仍有待确定。尽管它很受欢迎，由tSCS诱导的神经可塑性也仍未被广泛探索，特别是由于缺乏合适的动物模型来研究这种干预措施。因此，这项工作的基础是在大鼠模型中多次使用tSCS(多次tSCS)以SCI后痉挛为目标,并确定脊髓中发生的长期生理改善和解剖神经可塑性.这里,我们表明，在不完全（严重T9挫伤）SCI（1）大鼠中的多阶段tSCS减少反射亢进，（2）增加H反射的低频相关调制，（3）防止腰运动神经元中氯化钾共转运蛋白同工型2（KCC2）膜下调，和(4)通常增加电机输出，即，响应tSCS单脉冲的肌电图幅度，特别是伸肌。一起,这项工作表明,作为药物干预的替代方案,多节段tSCS可以靶向并减轻SCI后痉挛状态,并开始强调潜在的神经可塑性有助于其成功改善功能恢复.
