Although epidural spinal stimulation (ESS) results in promising therapeutic effects in individuals with spinal cord injury (SCI), its potential to generate functional motor recovery varies between individuals and remains largely unclear. However, both preclinical and clinical studies indicate the capacity of electrical and pharmacological interventions to synergistically increase the engagement of spinal sensorimotor networks and regain motor function after SCI. This study explored whether selective pharmacological antagonism of the adenosine A1 receptor subtype synergizes with ESS, thereby increasing motor response. We hypothesized that selective pharmacological antagonism of A1 receptors during ESS would produce facilitatory effects in spinal sensorimotor networks detected as an increased amplitude of spinally-evoked motor potentials and sustained duration of ESS induced activity. Terminal experiments were performed in adult rats using trains of stereotyped pulses at 40 Hz delivered at L5 with the local administration to the cord of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We demonstrated that ESS combined with the blockage of A1 receptors increased the magnitude of the endogenous modulation and postponed the decay of responses that occur during ESS alone. Although DPCPX significantly increased the yield of repetitive stimulation in intact spinal cords, the effects of A1 antagonism on motor evoked responses after an acute spinal transection was not detected. These studies support the future investigation of the optimal dosage, methods of delivery, and systemic effects of the synergistic application of A1 antagonists and spinal stimulation in the intact and injured spinal cord.

中文翻译：

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A1 腺苷受体的选择性拮抗作用加强了硬膜外脊髓刺激过程中感觉运动网络的神经调节

尽管硬膜外脊髓刺激 (ESS) 对脊髓损伤 (SCI) 的个体产生了有希望的治疗效果，但其产生功能性运动恢复的潜力因人而异，并且在很大程度上仍不清楚。然而，临床前和临床研究表明，电学和药理学干预能够协同增加脊髓感觉运动网络的参与并在 SCI 后恢复运动功能。本研究探讨了腺苷 A1 受体亚型的选择性药理学拮抗作用是否与 ESS 协同作用，从而增加运动反应。我们假设在 ESS 期间 A1 受体的选择性药理学拮抗会在脊髓感觉运动网络中产生促进作用，检测为脊髓诱发运动电位的振幅增加和 ESS 诱导活动的持续持续时间。使用在 L5 处传递的 40 Hz 定型脉冲序列在成年大鼠中进行终端实验，局部给药 8-环戊基-1,3-二丙基黄嘌呤 (DPCPX)。我们证明 ESS 与 A1 受体的阻断相结合增加了内源性调节的幅度并推迟了单独在 ESS 期间发生的反应的衰减。尽管 DPCPX 显着增加了完整脊髓中重复刺激的产量，未检测到 A1 拮抗剂对急性脊髓横断后运动诱发反应的影响。这些研究支持未来对 A1 拮抗剂协同应用和脊髓刺激在完整和受损脊髓中的最佳剂量、给药方法和全身效应的研究。