University of Pittsburgh, Department of Physical Medicine and Rehabilitation, Center for the Neural Basis of Cognition, Systems Neuroscience Institute, Pittsburgh, Pennsylvania 15261, USA.
J Neurosci. 2013 Jul 31;33(31):12898-907. doi: 10.1523/JNEUROSCI.1552-13.2013.
Baclofen is a GABAB receptor agonist commonly used to relief spasticity related to motor disorders. The effects of baclofen on voluntary motor output are limited and not yet understood. Using noninvasive transcranial magnetic and electrical stimulation techniques, we examined electrophysiological measures probably involving GABAB (long-interval intracortical inhibition and the cortical silent period) and GABAA (short-interval intracortical inhibition) receptors, which are inhibitory effects mediated by subcortical and cortical mechanisms. We demonstrate increased active long-interval intracortical inhibition and prolonged cortical silent period during voluntary activity of an intrinsic finger muscle in humans with chronic incomplete cervical spinal cord injury (SCI) compared with age-matched controls, whereas resting long-interval intracortical inhibition was unchanged. However, long-term (~6 years) use of baclofen decreased active long-interval intracortical inhibition to similar levels as controls but did not affect the duration of the cortical silent period. We found a correlation between signs of spasticity and long-interval intracortical inhibition in patients with SCI. Short-interval intracortical inhibition was decreased during voluntary contraction compared with rest but there was no effect of SCI or baclofen use. Together, these results demonstrate that baclofen selectively maintains use-dependent modulation of largely subcortical but not cortical GABAB neuronal pathways after human SCI. Thus, cortical GABA(B) circuits may be less sensitive to baclofen than spinal GABAB circuits. This may contribute to the limited effects of baclofen on voluntary motor output in subjects with motor disorders affected by spasticity.
巴氯芬是一种 GABA B 受体激动剂，常用于缓解与运动障碍相关的痉挛。巴氯芬对自主运动输出的影响是有限的，目前尚不清楚。使用非侵入性经颅磁和电刺激技术，我们检查了可能涉及 GABA B（长时程皮质内抑制和皮质静息期）和 GABA A（短时程皮质内抑制）受体的电生理指标，这些抑制效应是由皮质下和皮质机制介导的。我们在慢性不完全性颈脊髓损伤（SCI）患者的自主手指肌肉活动中，与年龄匹配的对照组相比，发现活性长时程皮质内抑制增加和皮质静息期延长，而静息长时程皮质内抑制不变。然而，长期（约 6 年）使用巴氯芬使活性长时程皮质内抑制降低至与对照组相似的水平，但不影响皮质静息期的持续时间。我们发现 SCI 患者的痉挛迹象与长时程皮质内抑制之间存在相关性。与休息时相比，主动收缩时短程皮质内抑制降低，但 SCI 或巴氯芬使用无影响。综上所述，这些结果表明，巴氯芬选择性地维持了人类 SCI 后，主要是皮质下而非皮质 GABA B 神经元通路的与使用相关的调制。因此，皮质 GABA（B）回路可能对巴氯芬的敏感性不如脊髓 GABA B 回路。这可能导致痉挛性运动障碍患者中，巴氯芬对自主运动输出的影响有限。
