Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden; Human Physiology Section of the DEPT, Università degli Studi di Milano, Milano I-20133, Italy.
Human Physiology Section of the DEPT, Università degli Studi di Milano, Milano I-20133, Italy.
Neuroscience. 2019 Apr 15;404:119-129. doi: 10.1016/j.neuroscience.2019.01.047. Epub 2019 Jan 31.
The aims of the study were to compare effects of baclofen, a GABA receptor agonist commonly used as an antispastic drug, on direct current (DC) evoked long-lasting changes in the excitability of afferent fibers traversing the dorsal columns and their terminal branches in the spinal cord, and to examine whether baclofen interferes with the development and expression of these changes. The experiments were performed on deeply anesthetized rats by analyzing the effects of DC before, during and following baclofen administration. Muscle and skin afferent fibers within the dorsal columns were stimulated epidurally and changes in their excitability were investigated following epidural polarization by 1.0-1.1 μA subsequent to i.v. administration of baclofen. Epidural polarization increased the excitability of these fibers during post-polarization periods of at least 1 h. The facilitation was as potent as in preparations that were not pretreated with baclofen, indicating that the advantages of combining epidural polarization with epidural stimulation would not be endangered by pharmacological antispastic treatment with baclofen. In contrast, baclofen-reduced effects of intraspinal stimulation combined with intraspinal polarization (0.3 μA) of terminal axonal branches of the afferents within the dorsal horn or in motor nuclei, whether administered ionophoretically or intravenously. Effects of DC on monosynaptically evoked synaptic actions of these fibers (extracellular field potentials) were likewise reduced by baclofen. The study thus provides further evidence for differential effects of DC on afferent fibers in the dorsal columns and the preterminal branches of these fibers and their involvement in spinal plasticity.
本研究旨在比较 GABA 受体激动剂巴氯芬(常用于抗痉挛药物)对穿过背柱的传入纤维及其在脊髓中的末梢分支的直流(DC)诱发的长时程兴奋性变化的影响,并探讨巴氯芬是否干扰这些变化的发展和表达。通过在给予巴氯芬前后分析 DC 的影响,在深度麻醉的大鼠上进行了实验。通过硬膜外刺激肌肉和皮肤传入纤维,并在静脉内给予巴氯芬后,用 1.0-1.1 μA 的硬膜外极化来分析它们的兴奋性变化。硬膜外极化在至少 1 小时的后极化期间增加了这些纤维的兴奋性。这种易化作用与未用巴氯芬预处理的制剂一样有效,表明将硬膜外极化与硬膜外刺激相结合的优势不会因巴氯芬的药理学抗痉挛治疗而受到威胁。相比之下,巴氯芬降低了脊髓内刺激与脊髓内极化(0.3 μA)的联合作用,这些传入纤维的末梢轴突分支位于背角或运动核内,无论是经离子电渗或静脉内给药。DC 对这些纤维的单突触诱发突触作用(细胞外场电位)的影响也被巴氯芬降低。因此,本研究进一步证明了 DC 对背柱传入纤维及其末梢分支的不同影响,并证明它们参与了脊髓可塑性。