脊髓损伤后丘脑神经元电生理特性及钠通道Nav1.3表达的变化
Changes in electrophysiological properties and sodium channel Nav1.3 expression in thalamic neurons after spinal cord injury.
作者信息
Hains Bryan C, Saab Carl Y, Waxman Stephen G
机构信息
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
出版信息
Brain. 2005 Oct;128(Pt 10):2359-71. doi: 10.1093/brain/awh623. Epub 2005 Aug 18.
Spinal cord contusion injury (SCI) is known to induce pain-related behaviour, as well as hyperresponsiveness in lumbar dorsal horn nociceptive neurons associated with the aberrant expression of Na(v)1.3, a rapidly repriming voltage-gated sodium channel. Many of these second-order dorsal horn neurons project to third-order neurons in the ventrobasal complex of the thalamus. In this study we hypothesized that, following SCI, neurons in the thalamus undergo electrophysiological changes linked to aberrant expression of Na(v)1.3. Adult male Sprague-Dawley rats underwent contusion SCI at the T9 thoracic level. Four weeks post-SCI, Na(v)1.3 protein was upregulated within thalamic neurons in ventroposterior lateral (VPL) and ventroposterior medial nuclei, where extracellular unit recordings revealed increased spontaneous discharge, afterdischarge, hyperresponsiveness to innocuous and noxious peripheral stimuli, and expansion of peripheral receptive fields. Altered electrophysiological properties of VPL neurons persisted after interruption of ascending spinal barrage by spinal cord transection above the level of the injury. Lumbar intrathecal administration of specific antisense oligodeoxynucleotides generated against Na(v)1.3 caused a significant reduction in Na(v)1.3 expression in thalamic neurons and reversed electrophysiological alterations. These results show, for the first time, a change in sodium channel expression within neurons in the thalamus after injury to the spinal cord, and suggest that these changes contribute to altered processing of somatosensory information after SCI.
脊髓挫伤损伤(SCI)已知会引发与疼痛相关的行为,以及与快速再激发电压门控钠通道Na(v)1.3异常表达相关的腰髓背角伤害性神经元的高反应性。许多这些二级背角神经元投射到丘脑腹侧基底复合体中的三级神经元。在本研究中,我们假设,脊髓损伤后,丘脑中的神经元会经历与Na(v)1.3异常表达相关的电生理变化。成年雄性Sprague-Dawley大鼠在T9胸段水平接受挫伤性脊髓损伤。脊髓损伤后四周,腹后外侧(VPL)和腹后内侧核的丘脑神经元内Na(v)1.3蛋白上调,细胞外单位记录显示自发放电增加、后放电、对无害和有害外周刺激的高反应性以及外周感受野扩大。在损伤水平以上进行脊髓横断以中断脊髓上行冲动后,VPL神经元改变的电生理特性仍然存在。对Na(v)1.3产生的特异性反义寡脱氧核苷酸进行腰段鞘内给药,可使丘脑神经元中Na(v)1.3表达显著降低,并逆转电生理改变。这些结果首次表明,脊髓损伤后丘脑中的神经元内钠通道表达发生变化,并表明这些变化导致脊髓损伤后体感信息处理改变。